RESUMEN
OBJECTIVE: To investigate the associations between markers of systemic and vascular inflammation, and indicators of vascular morphology and function. METHODS: In 59 apparently healthy individuals, we measured serum levels of highly sensitive C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Endothelium-dependent (EDV) and -independent (EIDV) vasodilatation was evaluated in the forearm by venous occlusion plethysmography and local infusions of methacholine and sodium nitroprussid. Endothelial function index (EFI) was expressed as the EDV/EIDV ratio. The intima-media thickness (IMT) of the common carotid artery was investigated with ultrasound (far wall). RESULTS: EFI was inversely related only to ICAM-1 (r=-0.31, P<0.02) by univariate analysis. This association remained significant after adjustment for age, sex, blood pressure, smoking and serum cholesterol. EFI did not relate to hsCRP, VCAM-1 or E-selectin. Neither hsCRP, nor the adhesion molecules were significantly related to carotid artery IMT. CONCLUSION: ICAM-1 was related to endothelial vasodilatory function, but not to IMT, suggesting that endothelial inflammatory activation is related to an impaired vascular relaxation in apparently healthy individuals.
Asunto(s)
Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Selectina E/sangre , Endotelio Vascular/inmunología , Molécula 1 de Adhesión Intercelular/sangre , Molécula 1 de Adhesión Celular Vascular/sangre , Vasodilatación/inmunología , Adulto , Anciano , Arteria Carótida Común/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Túnica Íntima/anatomía & histología , Túnica Íntima/inmunologíaRESUMEN
BACKGROUND: It is unclear if insulin-mediated vasodilatation is altered by ageing and if this affects insulin-mediated glucose uptake. MATERIAL AND METHODS: A 2-h euglycaemic hyperinsulinaemic clamp (56 mU m(-2) min(-1)) was performed in 10 healthy, nonobese elderly men (70-75 years) and 13 young men (23-28 years). Forearm blood flow (FBF) was measured by venous occlusion plethysmography and forearm glucose uptake was calculated by arterial and venous serum glucose determinations in the forearm. RESULTS: Insulin induced an increase in FBF in the younger men (from 3.9 +/- 1.1 SD to 5.9 +/- 2.2 mL min(-1) 100(-1)mL tissue, P < 0.001), but this insulin-mediated vasodilatation was completely blunted in the elderly subjects. Glucose extraction during the clamp was significantly higher in the elderly subjects (1.2 +/- 0.76 vs. 0.82 +/- 0.37 mmol L(-1) at 120 min, P < 0.01), resulting in a similar forearm glucose uptake in the two groups. On the other hand, whole-body glucose uptake was significantly decreased in the elderly subjects (5.3 +/- 1.8 vs. 8.0 +/- 1.1 mg kg(-1) min(-1), P < 0.001). CONCLUSION: The present study showed that the ability of insulin to induce vasodilatation is blunted in the forearm in healthy, nonobese elderly subjects. However, the elderly compensate for this impairment with an increased glucose extraction from arterial blood to maintain an unaltered forearm glucose uptake.
Asunto(s)
Envejecimiento/sangre , Envejecimiento/fisiología , Glucemia/metabolismo , Insulina/fisiología , Vasodilatación/fisiología , Adulto , Anciano , Velocidad del Flujo Sanguíneo/fisiología , Antebrazo , Técnica de Clampeo de la Glucosa , Humanos , Resistencia a la Insulina/fisiología , MasculinoRESUMEN
OBJECTIVES: To investigate if antihypertensive treatment could improve endothelium-dependent vasodilatation in hypertensive patients, and whether the angiotensin II subtype-1 (AT1)-receptor antagonist irbesartan and the beta1-receptor antagonist atenolol would differ in this respect. SUBJECTS AND METHODS: Thirty-four patients (28 men and six women) with mild-to-moderate essential hypertension (diastolic blood pressure 90-120 mmHg) were randomized to once daily 150-300 mg irbesartan or 50-100 mg atenolol in a double-blind fashion, preceded by a placebo run-in period. Forearm blood flow (FBF) was assessed by venous occlusion plethysmography during local intra-arterial infusions of methacholine and sodium nitroprusside, to evaluate endothelium-dependent and endothelium-independent vasodilatation, respectively. Measurements of FBF were undertaken at the end of the run-in placebo period and repeated after 3 months of active antihypertensive treatment. RESULTS: Irbesartan and atenolol induced a similar decline in blood pressure (from 171/107 to 158/98 mmHg, P < 0.05), and improved endothelium-dependent vasodilatation (e.g. an increase in FBF response to 4 microg/min methacholine from 325 +/- 29% to 411 +/- 41%, P < 0.05), with no difference between the two study drugs. No significant changes in endothelium-independent vasodilatation were induced by irbesartan or by atenolol. CONCLUSIONS: The present study shows that 3 months of antihypertensive therapy with irbesartan or atenolol improves endothelium-dependent vasodilatation.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Antihipertensivos/uso terapéutico , Atenolol/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Tetrazoles/uso terapéutico , Antagonistas de Receptores de Angiotensina , Método Doble Ciego , Femenino , Antebrazo/irrigación sanguínea , Humanos , Irbesartán , Masculino , Persona de Mediana Edad , Receptor de Angiotensina Tipo 1 , Flujo Sanguíneo Regional/efectos de los fármacos , Vasodilatación/efectos de los fármacosRESUMEN
The fatty acid (FA) composition of the serum lipids has been associated with cardiovascular disease (CVD). As an attenuated endothelium-dependent vasodilation (EDV) has been suggested as an early marker of atherosclerosis, we investigated the relationships between the proportion of FA in serum lipids (cholesterol esters and phospholipids) together with the levels of serum LDL- and HDL-cholesterol and triglycerides and EDV, as well as endothelium-independent vasodilation (EIDV). Fifty-six healthy subjects (31 men and 25 women), aged between 20 and 69 years, underwent measurements of forearm blood flow (FBF) at rest and during local infusion of 2 and 4 microg/min of metacholine (Mch, evaluating EDV), 5 and 10 microg/min of sodium nitroprusside (SNP, evaluating endothelium-independent vasodilation, EIDV) using venous occlusion plethysmography. An index of endothelial function was calculated as the ratio between EDV and EIDV. The proportion of palmitic (16:0) and palmitoleic (16:1) acids were inversely related (r=-0.35 and -0.35, P<0.01 for both), while linoleic acid (18:2 n6) and the HDL-cholesterol concentration were positively related (r=0.35 and 0.36, P<0.01 for both) to the endothelial function index. In multiple regression analysis also including age and gender, palmitoleic acid and HDL-cholesterol were significant independent predictors of endothelial function. Alfa-linolenic acid (18:3 n3) was positively correlated to both EDV and EIDV (r=0.40 and 0.43, P<0.01 for both), indicating a protective effect of this essential FA on vasodilation in general. It is concluded that the FA composition of serum lipids, partly reflecting the composition of dietary fat and previously associated with the development of CVD, was associated with endothelial function in apparently healthy subjects.
Asunto(s)
HDL-Colesterol/sangre , LDL-Colesterol/sangre , Endotelio Vascular/metabolismo , Ácidos Grasos/sangre , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología , Vasodilatadores/administración & dosificación , Adulto , Anciano , Velocidad del Flujo Sanguíneo , Estudios Transversales , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Femenino , Humanos , Infusiones Intravenosas , Modelos Lineales , Masculino , Cloruro de Metacolina/administración & dosificación , Persona de Mediana Edad , Nitroprusiato/administración & dosificación , Pletismografía , Radioinmunoensayo , Valores de Referencia , Análisis de Regresión , Sensibilidad y EspecificidadRESUMEN
1. Endothelial dysfunction is seen in patients with essential hypertension or congestive heart failure (CHF). The present study aimed to evaluate the direct effect on endothelium- dependent vasodilation (EDV) of different pharmacological drugs commonly used in the treatment of these conditions. 2. Forearm blood flow (FBF) was measured in 37 young healthy normotensive subjects with venous occlusion plethysmography during local intra-arterial infusions of methacholine (MCh; 2-4 microg/min), evaluating EDV, and sodium nitroprusside (SNP; 5-10 microg/min), evaluating endothelium-independent vasodilation (EIDV). The measurements of EDV and EIDV were undertaken under baseline conditions and were repeated after 1 h intra-arterial infusion of digoxin (0.1 mg/h), furosemide (5.0 mg/h), enalaprilat (2,4 mg/h), metoprolol (1.2 mg/h) or saline (controls). 3. Enalaprilat and digoxin improved the FBF response to MCh at 4 microg/min (from 22.7+/-2.3 to 25.5+/-2.1 mL/min per 100 mL tissue (P < 0.01) and from 18.2+/-2.4 to 22.2+/-2.0 mL/min per 100 mL tissue (P < 0.05), respectively). No significant changes where induced by furosemide or metoprolol in response to MCh at 4 microg/min (from 19.4+/-2.0 to 22.9+/-2.8 and from 15.3+/-2.4 to 14.7+/-1.1 mL/min per 100 mL tissue, respectively). No significant changes in basal FBF or EIDV were induced by the different drugs. When the endothelial function index was calculated as the MCh: SNP FBF ratio, a significant improvement was seen only with enalaprilat (1.1+/-0.1 to 1.2+/-0.1; P < 0.01) and furosemide (1.0+/-0.1 to 1.3+/-0.4; P < 0.05). 4. In conlusion, the results of the present study show that enalaprilat and furosemide improve endothelial vasodilatory function, while no major effect was induced by digoxin or metoprolol. Thus, different direct effects on the endothelium in young normotensive subjects were induced by drugs commonly used in the treatment of hypertension or CHF.
Asunto(s)
Antihipertensivos/farmacología , Cardiotónicos/farmacología , Digoxina/farmacología , Diuréticos/farmacología , Enalaprilato/farmacología , Endotelio Vascular/efectos de los fármacos , Furosemida/farmacología , Metoprolol/farmacología , Adolescente , Adulto , Antebrazo/irrigación sanguínea , Humanos , Flujo Sanguíneo Regional/efectos de los fármacosRESUMEN
BACKGROUND: Our aim was to test the hypothesis that genes encoding components in the renin-angiotensin system influence endothelial vasodilatory function. METHODS: In 59 apparently healthy, normotensive individuals, endothelium-dependent vasodilation (EDV) and endothelial-independent vasodilation (EIDV) was evaluated by infusing metacholine and sodium nitroprusside into the brachial artery. Forearm blood flow was measured by venous occlusion plethysmography. The ACE insertion (I)/deletion (D) polymorphism, the T174M and M235T angiotensinogen restriction fragments length polymorphisms, the angiotensin II receptor type 1 (AT1R) A1166C, and the aldosterone synthase gene (CYP11B2) C-344T polymorphisms were analysed. RESULTS: When analysing the ACE, the two angiotensinogen and the aldosterone synthase CYP11B2 genotypes independently, no significant association with endothelial vasodilatory function was found. However, a significant reduction in endothelium-dependent vasodilation was observed in the subjects (n=9) with the ACE D allele and the angiotensinogen T174M genotype (P<0.05). Subjects with the AT1R genotype AC showed a reduction in both EDV (P=0.05) and EIDV (P=0.04) when compared with those with the AA genotype. CONCLUSIONS: The subjects with the ACE D allele in combination with the angiotensinogen T174M genotype are associated with a reduced EDV. This together with the observation that the AC AT1R genotype is associated with a reduction in both EDV and EIDV, supports the hypothesis that endothelial vasodilatory function is influenced by genes in the renin-angiotensinogen system.
Asunto(s)
Endotelio Vascular/fisiología , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Sistema Renina-Angiotensina/genética , Adulto , Anciano , Citocromo P-450 CYP11B2/genética , Femenino , Eliminación de Gen , Humanos , Masculino , Persona de Mediana Edad , Nitroprusiato/administración & dosificación , Nitroprusiato/farmacología , Polimorfismo de Longitud del Fragmento de Restricción , Receptor de Angiotensina Tipo 1 , Receptor de Angiotensina Tipo 2 , Receptores de Angiotensina/genéticaRESUMEN
Dyslipidaemia, with elevations of circulating triacylglycerols (triglycerides) and non-esterified (free) fatty acids, and hyperinsulinaemia are often found in the same subjects, the so-called 'insulin resistance syndrome'. The present study aims to investigate how elevated levels of non-esterified fatty acids, hyperinsulinaemia and the combination of these factors affects endothelium-dependent vasodilatation (EDV). Ten volunteers were examined on two occasions. Intralipid (plus heparin) or saline (0.9% NaCl) was infused for 4 h. During the final 2 h, euglycaemic hyperinsulinaemia (80+/-4 m-units/l) was imposed. EDV and endothelium-independent vasodilatation were evaluated in the forearm by local intra-arterial infusion of methacholine or sodium nitroprusside at baseline and after 2 and 4 h. Forearm blood flow was measured by venous occlusion plethysmography. Lipid oxidation was determined by measuring plasma malondialdehyde levels. Infusion of Intralipid plus heparin increased the concentration of non-esterified fatty acids to 2.6+/-1.2 mmol/l and decreased EDV from 27.6+/-8.7 to 21.0+/-5.7 ml x min(-1) x 100 ml(-1) tissue (P < 0.01). This effect was completely reversed by hyperinsulinaemia (P < 0.01). Hyperinsulinaemia alone increased EDV (to 30.4+/-9.5 ml x min(-1) x 100 ml(-1) tissue; P < 0.01), while endothelium-independent vasodilatation was unaltered by the interventions. Infusion of Intralipid plus heparin increased malondialdehyde levels from 0.67+/-0.22 to 1.2+/-0.37 micromol/l (P < 0.001), while hyperinsulinaemiadid not change the malondialdehyde level. In conclusion, an acute increase in serum levels of non-esterified fatty acids increased lipid oxidation and decreased EDV. The effect on EDV of non-esterified fatty acids could be reversed by hyperinsulinaemia.
Asunto(s)
Endotelio Vascular/fisiopatología , Ácidos Grasos no Esterificados/fisiología , Hiperinsulinismo/fisiopatología , Vasodilatación/fisiología , Adulto , Endotelio Vascular/efectos de los fármacos , Emulsiones Grasas Intravenosas/farmacología , Ácidos Grasos no Esterificados/sangre , Femenino , Antebrazo/irrigación sanguínea , Técnica de Clampeo de la Glucosa , Humanos , Hiperinsulinismo/sangre , Masculino , Malondialdehído/sangre , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , Triglicéridos/sangre , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacologíaRESUMEN
Using both in vitro and in vivo techniques, it has repeatedly been shown that endothelium-dependent vasodilation (EDV) is impaired in different forms of experimental hypertension (SHR, Dahl salt-sensitive rat, DOCA-salt rat and renovascular hypertension). EDV has also been found to be impaired in primary, as well as in secondary forms of human hypertension. Although impaired EDV is a general finding in hypertension, the pathophysiological mechanisms might differ between different forms of hypertension and between different types of vessels and vascular beds. Impaired activity of nitric oxide synthase, increased release of endothelin-1, increased production of a prostanoid-derived contracting factor, decreased generation of endothelium-derived hyperpolarizing factor/s and impairment caused by superoxide ions have all been shown to contribute to the impairment of EDV during different conditions. While most antihypertensive treatments improve EDV in experimental hypertension, no uniform picture has been seen in human hypertension, possibly because different antihypertensive drugs have different direct actions on EDV. This review shows that while impaired EDV has been found to be a general feature of hypertension, the mechanisms involved and the therapeutic opportunities have still to be established.
Asunto(s)
Endotelio Vascular/fisiopatología , Hipertensión/fisiopatología , Vasodilatación , Animales , Circulación Sanguínea , Endotelinas/fisiología , Humanos , Óxido Nítrico/fisiologíaRESUMEN
Endothelial function is important for local vascular regulation and an abnormal endothelium-dependent vasodilatation (EDV) has been observed in subjects with essential hypertension. As ambulatory blood pressure (ABP) is more closely related to target organ damage than office blood pressure, this study investigated also if 24-h ABP is more closely related to an impaired EDV than office blood pressure recordings. In a group of 25 untreated patients with essential hypertension and an age- and sex-matched control group (n = 21) endothelial function was evaluated by measurements of forearm blood flow (FBF) during local intra-arterial infusions of metacholine (evaluating EDV) and sodium nitroprusside (evaluating endothelium independent vasodilation, EIDV). FBF was measured with venous occlusion plethysmography. Both office mean artery pressure (MAP; r= -0.57, p < 0.001) and 24-h ABP (r = 0.40, p < 0.01) were related to the endothelial vasodilator function (EDV to EIDV ratio) in an inverse way, but ABP was not superior to office blood pressure recordings. Within the hypertensive group, pronounced white-coat effect (office minus daytime ABP) was associated with a reduced,EDV (r= 0.41, p < 0.05). The degree of night-time decline in blood pressure ("dipping") showed no correlation to EDV. In conclusion, the finding that ABP was no more closely related to the endothelial vasodilator function than office blood pressure recordings might be due to an increased mental alertness affecting EDV in some hypertensive subjects, as suggested by the finding of a reduced EDV in those with a pronounced white-coat effect.
Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Presión Sanguínea , Endotelio Vascular/fisiopatología , Hipertensión/fisiopatología , Vasodilatación , Determinación de la Presión Sanguínea/métodos , Ritmo Circadiano , Femenino , Antebrazo/irrigación sanguínea , Humanos , Hipertensión/psicología , Masculino , Cloruro de Metacolina/farmacología , Persona de Mediana Edad , Donantes de Óxido Nítrico/farmacología , Nitroprusiato/farmacología , Consultorios Médicos , Pletismografía/métodos , Flujo Sanguíneo Regional/efectos de los fármacos , Estrés Psicológico/complicacionesRESUMEN
OBJECTIVE: The aim of this study was to evaluate the direct effect of three principally different beta-receptor blocking agents on endothelium-dependent vasodilatation (EDV) in the human forearm. METHODS: In 27 young normotensive subjects forearm blood flow (FBF) was measured with venous occlusion plethysmography during local intra-arterial infusions of methacholine (MCh), evaluating EDV, and sodium nitroprusside (SNP), evaluating endothelium-independent vasodilatation (EIDV). The measurements of EDV and EIDV were undertaken at baseline conditions and repeated after 1 h of concomitant intra-arterial infusion of atenolol (n = 8, 1.2 mg/h), propranolol (n = 7, 1.2 mg/h), labetalol (n = 7, 16 mg/h) or saline (n = 5). RESULTS: The selective beta-blocker atenolol showed a tendency to improve the FBF response to MCh (from 28.8 +/- 9.2 to 32.6 +/- 8.7 ml/min/ml tissue, p < 0.05). The nonselective beta-blocker propranolol attenuated the FBF response to MCh significantly (from 30.5 +/- 6.7 to 22.8 +/- 4.5 ml/min/ml tissue, p < 0.01). In these groups baseline FBF and EIDV were unchanged. Labetalol, a combined non-selective beta-blocker and selective alpha-1-blocker, increased baseline FBF and increased the response to both MCh and SNP in parallel (p < 0.05 for MCh and p = 0.07 for SNP). Saline did not change baseline FBF, EDV or EIDV. CONCLUSIONS: This study showed that local infusion of different beta-blocking agents in normotensive subjects affects endothelial vasodilatory function differently. This technique could be used to evaluate the direct effect of vasoactive drugs on EDV.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Antihipertensivos/farmacología , Atenolol/farmacología , Endotelio Vascular/fisiología , Antebrazo/irrigación sanguínea , Labetalol/farmacología , Nitroprusiato/farmacología , Propranolol/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Antagonistas Adrenérgicos alfa/farmacología , Adulto , Antiinflamatorios no Esteroideos/farmacología , Presión Sanguínea/efectos de los fármacos , Diclofenaco/farmacología , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Inyecciones Intraarteriales , Masculino , Cloruro de Metacolina , Pletismografía , Receptores Adrenérgicos alfa 1/efectos de los fármacos , Receptores Adrenérgicos alfa 1/fisiología , Receptores Muscarínicos/efectos de los fármacos , Vasodilatación/fisiologíaRESUMEN
To investigate the relationship between left ventricular hypertrophy (LVH) and endothelium-dependent vasodilation (EDV), 30 untreated hypertensive patients, 18 treated hypertensives (53 +/- 7 years, all males) and 26 age-and sex-matched healthy normotensive controls, underwent evaluation of EDV and endothelium-independent vasodilation (EIDV) in the forearm, by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium nitroprusside (SNP, evaluating EIDV). Forearm blood flow was measured by venous occlusion plethysmography and LVH was measured by echocardiography. The reduction in forearm vascular resistance during MCh infusion (4 microg/min) was significantly smaller in the hypertensive patients with LVH when compared to those without LVH, both in the untreated (-61 +/- 12%, n = 19 vs -72 +/- 4%, n = 11, p < 0.01) and in the treated group (-60 +/- 15%, n = 11 vs -75 +/- 5%, n = 7, p < 0.01). Thereby, EDV was significantly impaired only in the hypertensive patients with LVH when compared to controls (-77 +/- 7% at MCh 4 microg/min, p < 0.001). EIDV was not significantly different between patients with and without LVH and controls. In conclusion, the presence of LVH was related to endothelial dysfunction, both in untreated and treated hypertensive patients, suggesting either a role for endothelial function in the development of LVH, or that a dysfunctional endothelium and LVH are coexisting markers of a more severe hypertensive disease.
Asunto(s)
Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/fisiopatología , Vasodilatación/fisiología , Adulto , Factores de Edad , Análisis de Varianza , Ecocardiografía , Endotelio Vascular/fisiopatología , Antebrazo/irrigación sanguínea , Humanos , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/complicaciones , Masculino , Análisis por Apareamiento , Cloruro de Metacolina/administración & dosificación , Cloruro de Metacolina/farmacología , Persona de Mediana Edad , Nitroprusiato/administración & dosificación , Nitroprusiato/farmacología , Pletismografía , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , Vasodilatación/efectos de los fármacosRESUMEN
It has repeatedly been shown that endothelium-dependent vasodilatation (EDV) is impaired in patients with untreated hypertension. The effect of antihypertensive treatment on EDV has, however, not been extensively investigated. In the present study, EDV and endothelium-independent vasodilatation (EIDV) were studied in 20 untreated and 41 treated hypertensive subjects and in 26 matched, normotensive controls by means of infusion of methacholine (MCh), 2 and 4 microg/min, evaluating EDV, and nitroprusside (SNP), 5 and 10 microg/min, evaluating EIDV, in the brachial artery. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The vasodilatory action of MCh was impaired in untreated hypertensives compared with controls, with the response in the treated hypertensives in between the other two groups (p < 0.01 vs both of the other groups). EIDV, on the other hand, was enhanced in the treated hypertensives (p < 0.01), so that the MCh to SNP FBF ratio, an index of endothelial function, was attenuated in both treated and untreated hypertensives (0.97 +/- 0.24 and 0.96 +/- 0.15, respectively), compared with controls (1.27 +/- 0.29, p < 0.001). Both EDV and EIDV declined with increasing number of antihypertensive drugs used in the treated hypertensives (p < 0.05). In conclusion, the endothelial function index was found to be similarly depressed in both treated and untreated hypertensive subjects compared with normotensive controls. Antihypertensive therapy seems to improve the vasodilatory capacity in general rather than enhancing endothelial function.
Asunto(s)
Antihipertensivos/uso terapéutico , Endotelio Vascular/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Vasodilatación/efectos de los fármacos , Análisis de Varianza , Antebrazo/irrigación sanguínea , Humanos , Persona de Mediana Edad , Flujo Sanguíneo Regional , Resistencia Vascular/fisiologíaRESUMEN
The aim of this study was to evaluate possible associations between endothelium-dependent vasodilatation (EDV) and cardiovascular structure and function. EDV could influence peripheral resistance and be affected by atherosclerosis and might thereby influence indices of cardiovascular structure and function. In a group of 31 apparently healthy men and 25 women (age range 20-69 years), EDV was evaluated by infusion of metacholine (4 micrograms min-1), and endothelium-independent vasodilatation (EIDV) was assessed by nitroprusside infusion (SNP, 10 micrograms min-1) in the brachial artery. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Left ventricular (LV) geometry and function and the intima-media thickness in the carotid artery were assessed by ultrasonography. The stroke index to pulse pressure ratio was used to evaluate arterial compliance. Several indices of cardiovascular structure and function were found to be related to an index of endothelial function, the EDV to EIDV ratio. Furthermore, left ventricular mass (LVM), the atrio-ventricular plane displacement, E/A ratio, IVRT, the intima-media thickness of the carotid artery and arterial compliance were all significantly related to both EDV and EIDV in women. However, most indices of cardiovascular structure and function, as well as endothelial function, change with age and only the relation between LV diastolic function and endothelial function in men remained significant (P < 0.05) after including age in multiple regression analysis. Age was related to both cardiovascular structure and function, as well as to endothelial function. Multiple regression analysis showed that ageing generally affects cardiovascular characteristics and endothelial function in parallel in these healthy subjects.
Asunto(s)
Envejecimiento/fisiología , Endotelio Vascular/fisiología , Vasodilatación/fisiología , Función Ventricular Izquierda/fisiología , Adulto , Anciano , Presión Sanguínea/fisiología , Arterias Carótidas/fisiología , Diástole/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Flujo Sanguíneo Regional , Sístole/fisiología , Resistencia Vascular/fisiologíaRESUMEN
OBJECTIVES: A progressive decline in endothelium-dependent vasodilation (EDV) in the human forearm with age has previously been reported. The aim of this study was to evaluate the interplay between age, gender and metabolic factors on EDV in healthy subjects in a population-based study. SETTING: Tertiary university hospital. SUBJECTS AND DESIGN: Thirty-six healthy men and 30 women, aged 20-69 years, underwent measurements of forearm blood flow (FBF) at rest and during local infusions of 2 and 4 microg min-1 of metacholine (evaluating EDV) and 5 and 10 microg min-1 of sodium nitroprusside (evaluating endothelium-independent vasodilation, EIDV) and during reactive hyperaemia by venous occlusion plethysmography. RESULTS: Age was inversely related to EDV (r = - 0.41, P < 0.05 in men; r = - 0.61, P < 0.01 in women) and maximal FBF during reactive hyperaemia in both men and women. EIDV was significantly related to age in an inverse way in women only. EDV was more pronounced in females than in males before menopause (48 +/- 3 SD years, 635 +/- 186 vs. 502 +/- 269% in males, P < 0.05), but similar in women and men thereafter (374 +/- 141 vs. 370 +/- 185% in men). The slope of the regression line for the relationship between age and EDV was flatter in premenopausal than in postmenopausal women (- 2.3 vs. - 6.4), whilst this slope was similar in younger and older men (- 5.5 vs. - 5.3). In multiple regression analysis, fasting blood glucose levels and the waist/hip ratio remained the only significant predictors of EDV in men (P < 0.01 for both), whilst age was the only significant independent predictor of EDV in women (P < 0.01). CONCLUSION: The interplay between age and metabolic factors as determinants of endothelial function is different in healthy men and women.
Asunto(s)
Envejecimiento/fisiología , Endotelio Vascular/metabolismo , Vasodilatación/fisiología , Adulto , Anciano , Envejecimiento/metabolismo , Análisis de Varianza , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Femenino , Antebrazo/irrigación sanguínea , Humanos , Hiperemia/fisiopatología , Masculino , Cloruro de Metacolina , Persona de Mediana Edad , Nitroprusiato , Parasimpaticomiméticos , Pletismografía/métodos , Valores de Referencia , Caracteres Sexuales , Vasodilatación/efectos de los fármacos , VasodilatadoresRESUMEN
UNLABELLED: Endothelium-dependent vasodilatation (EDV) in humans has been evaluated mainly by local infusion of a muscarinic-receptor agonists in the forearm. It has been postulated that the function of the vasodilator nitric oxide (NO) can be evaluated with this technique. However, the role of the vasoconstrictor endothelin in this model has not been investigated. METHODS: Ten male hypertensive and seven male normotensive subjects were subjected to measurements of forearm blood flow (FBF) by venous occlusion plethysmography during local intra-arterial infusion of metacholine (4 microg/min) or nitroprusside (10 microg/min). In parallel, forearm venous plasma endothelin (ir-ET) was determined. RESULTS: Metacholine and nitroprusside increased FBF 2.3 and 2.2 times the baseline level (6.6+/-2.8 SD ml/min/100 ml tissue) in hypertensive subjects and 5.1 times the baseline level (2.7+/-3.0 ml/min/100 ml tissue) for both drugs in the normotensive subjects. None of the drugs induced any significant changes in ir-ET levels in any of the groups (baseline 1.5+/-0.4 pmol/l in hypertensive and 1.1+/-1.2 pmol/l in normotensive subjects). However, in the hypertensive subjects, the individual change in venous ir-ET levels during infusion with metacholine, but not with nitroprusside, was inversely related to the degree of vasodilatation induced by this agent (r = -0.71, p < 0.02). A similar correlation coefficient (r=-0.69) was found in healthy subjects. CONCLUSION: Muscarinic-receptor-agonist-stimulated vasodilatation in the human forearm, thought mainly to reflect NO synthesis, was inversely related to the change in endothelin levels, suggesting an important role for this endothelium-derived vasoconstrictor in this model of EDV.
Asunto(s)
Endotelinas/fisiología , Endotelio Vascular/fisiología , Antebrazo/irrigación sanguínea , Vasodilatación , Adulto , Anciano , Endotelinas/sangre , Humanos , Masculino , Cloruro de Metacolina/farmacología , Persona de Mediana Edad , Óxido Nítrico/fisiología , Vasodilatación/efectos de los fármacosRESUMEN
Insulin is known to increase blood flow in parallel to glucose uptake in skeletal muscle. However, it is not known if an increase in blood flow by itself is associated with an increase in glucose uptake in the absence of hyperinsulinemia. To investigate further this matter, the effect of increased blood flow on forearm glucose uptake was studied in the fasting state during intra-arterial infusions of two different vasodilators, metacholine and nitroprusside, in 19 hypertensive subjects. Both metacholine (4 microg/min) and nitroprusside (10 microg/min) increased resting forearm blood flow, measured by venous occlusion plethysmography, to a similar degree (180 % and 170 %, respectively, p<0.0001 for both). However, metacholine infusion increased the forearm glucose uptake from 2.0+/-0.9 (S.D.) during rest to 5.5+/-3.0 umol/min/100 ml tissue (p<0.0001), while no significant change in glucose uptake was seen during nitroprusside infusion (2.3+/-1.4 micromol/min/100 ml tissue). In conclusion, vasodilatation induced by metacholine, but not by nitroprusside, increased glucose uptake in the forearm of hypertensive patients. Thus, an increase in forearm blood flow does not necessarily improve glucose uptake in the forearm during the fasting state.
Asunto(s)
Glucemia/metabolismo , Antebrazo/irrigación sanguínea , Cloruro de Metacolina/farmacología , Nitroprusiato/farmacología , Vasodilatadores/farmacología , Adulto , Anciano , Velocidad del Flujo Sanguíneo , Ayuno , Humanos , Hipertensión/fisiopatología , Cinética , Masculino , Persona de Mediana Edad , Músculo Esquelético/metabolismo , Consumo de OxígenoRESUMEN
Due to the reported associations between a low intake of vitamin E and atherosclerosis on one hand, and between endothelial dysfunction and atherosclerosis on the other hand, we investigated the relationship between endothelium-dependent vasodilation and serum levels of vitamin E (alpha- and gamma-tocopherol) as well as the lipid peroxidation markers malondialdehyde and 8-iso-PGF(2alpha) in a healthy population. Healthy subjects (31 men and 25 women), aged between 20 and 69 years, underwent measurements of forearm blood flow (FBF) at rest and during local infusion of 2 and 4 microg/min of methacholine (Mch, to evaluate endothelium-dependent vasodilation) and 5 and 10 microg/min of sodium nitroprusside (SNP, to evaluate endothelium-independent vasodilation, and during reactive hyperemia using venous occlusion plethysmography. Serum alpha-tocopherol concentration was significantly related to the index of endothelial function (r = 0.46, p < 0.01), defined as the ratio between the maximal dilatations during Mch and SNP infusions. Serum gamma-tocopherol levels were positively related to the maximal FBF during reactive hyperemia (r = 0.54, p < 0.01) in women only. Furthermore, in women only, plasma 8-iso-PGF(2alpha) levels were inversely related to the relative increases in FBF during both Mch and SNP infusions (r = -0.58 and r = -0.59, p < 0.01 for both). The results show a relationship between the levels of alpha-tocopherol and endothelial vasodilatory function, suggesting a beneficial role for this potent lipid-soluble antioxidant also in a population sample of apparently healthy subjects. Furthermore, in women, the accumulation of lipid peroxidation products such as 8-iso-PGF(2alpha) seems to be associated with an impaired vasodilation in general.
Asunto(s)
Dinoprost/análogos & derivados , Endotelio Vascular/fisiología , Vitamina E/sangre , Adulto , Anciano , Dinoprost/sangre , F2-Isoprostanos , Femenino , Humanos , Peroxidación de Lípido/fisiología , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Vasodilatación/fisiologíaRESUMEN
1. Previous investigations have demonstrated an impaired endothelium-dependent vasodilatation (EDV) in patients with hypertension. The present study aimed to investigate if an acute rise in blood pressure to hypertensive levels impairs EDV in otherwise normotensive subjects. 2. Twenty-seven young, healthy, normotensive subjects were studied. Eight of these underwent evaluation of EDV and endothelium-independent vasodilatation (EIDV) by means of forearm blood flow measurements during local intra-arterial infusions of methacholine (2 and 4 micrograms/min) and sodium nitroprusside (5 and 10 micrograms/min), before and after 1 h of sustained hypertension, induced by noradrenaline given intravenously. Identical measurements were made in 11 subjects before and during concomitant local intra-arterial infusion of noradrenaline without change in blood pressure and eight subjects were studied during saline infusions. 3. One hour of sustained hypertension (diastolic blood pressure > 95 mmHg) significantly attenuated both forearm blood flow (17.4 +/- 6.8 versus 27.4 +/- 6.8 ml.min-1.100 ml-1 tissue at baseline, P < 0.05) and forearm vascular resistance decrease (3.2 +/- 0.87 versus 7.4 +/- 2.5 units at baseline, P < 0.05) during methacholine infusion. These attenuations were significantly more pronounced for methacholine than for sodium nitroprusside (P < 0.05). In contrast, local intra-arterial noradrenaline infusions impaired vasodilatation induced by methacholine and sodium nitroprusside to a similar extent. Saline infusions did not change either EDV or EIDV. 4. Thus, an acute rise in blood pressure to hypertensive levels induced by noradrenaline impaired EDV more than EIDV in otherwise normotensive subjects, while no such selective effect of local noradrenaline was seen, suggesting that a high blood pressure impairs endothelial vasodilator function.
Asunto(s)
Endotelio Vascular/fisiopatología , Hipertensión/fisiopatología , Cloruro de Metacolina/farmacología , Nitroprusiato/farmacología , Vasodilatadores/farmacología , Enfermedad Aguda , Adulto , Endotelio Vascular/efectos de los fármacos , Femenino , Antebrazo/irrigación sanguínea , Humanos , Hipertensión/inducido químicamente , Infusiones Intraarteriales , Masculino , Norepinefrina/farmacologíaRESUMEN
The present study aimed to investigate the influence of the angiotensin-converting enzyme (ACE)-inhibitor captopril and the Ca-antagonist nifedipine on endothelium-dependent vasodilation (EDV) in the forearm of hypertensive patients. Twenty-three middle-aged untreated hypertensive patients underwent evaluation of EDV and endothelium-independent vasodilation (EIDV) in the forearm, by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium-nitroprusside (SNP, evaluating EIDV), before and 1 h after intake of either captopril (25 mg) or nifedipine (10 mg) in a randomised, double-blind fashion. A matched normotensive control group was investigated at baseline conditions only. Five of the hypertensives were also evaluated after 3 months of treatment with captopril 25 mg twice daily in an open pilot study. First, the vasodilation induced by methacholine (MCh), but not SNP, was significantly attenuated in the hypertensive patients compared to the normotensive controls (P < 0.001 at MCh 4 microg/min). Second, although the two drugs induced a similar decline in blood pressure (BP) 1 h after administration (-11 to 10 mm Hg/-8 to 7 mm Hg), captopril significantly potentiated the vasodilator response to MCh (+32+/-13%, MCh 4 micr og/min, P < 0.01) but not SNP, while nifedipine did not significantly alter the response to either MCh or SNP. The improvement in vasodilator response to MCh induced by captopril was closely related to the reduction in BP (r = 0.72, P < 0.01). Third, in the pilot study, 3 months of captopril treatment induced a significant potentiation of the vasodilator response to MCh (+34+/-17%, MCh 4 microg/min, P < 0.05) in parallel with a significant BP reduction (-22+/-24/13+/-13 mm Hg, P < 0.05), while the response to SNP was unchanged. In conclusion, the present study confirmed that essential hypertension is associated with a defect in EDV. Furthermore, an improvement in EDV was seen in hypertensive patients shortly after administration of captopril, but not nifedipine. In addition, a significant beneficial effect on EDV was seen in a small pilot study during long-term treatment with captopril.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Captopril/farmacología , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Nifedipino/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Arterias/fisiopatología , Bloqueadores de los Canales de Calcio/farmacología , Bloqueadores de los Canales de Calcio/uso terapéutico , Captopril/uso terapéutico , Método Doble Ciego , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Femenino , Antebrazo/irrigación sanguínea , Humanos , Masculino , Persona de Mediana Edad , Nifedipino/uso terapéutico , Vasodilatadores/uso terapéuticoRESUMEN
Several studies indicated an abnormal endothelium-dependent vasodilation (EDV) in hypertensive patients, but no study has systematically investigated the effects of different pharmacologic classes of antihypertensive drugs on EDV. This study aimed to evaluate the effects of three different antihypertensive regimens [angiotensin-converting enzyme (ACE) inhibition, calcium channel blockade, and beta-blockade] on EDV when given locally in the forearm at a constant blood pressure. The increase in forearm blood flow (FBF) during local intraarterial infusions of methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; inducing endothelium-independent vasodilation, EIDV) was measured in young, normotensive subjects by venous occlusion plethysmography, before and during concomitant local intraarterial infusion of any of the antihypertensive drugs. Without changing baseline FBF, enalaprilat (n=6, 2.4 mg/h) potentiated the increase in FBF induced by MCh [from 22.6+/-2.3 (SD) to 25.4+/-2.3 ml/min/100 ml tissue at 4 microg/min; p < 0.05], but the response to SNP was unchanged. Local intraarterial verapamil infusion (n=6), at a dose individually titrated to keep baseline FBF unchanged, did not alter the response to MCh infusion, whereas the response to SNP was potentiated. A higher dose of verapamil (n=6), which increased baseline FBF, increased both EDV and EIDV significantly in parallel (p < 0.05). The local propranolol infusion (n=6, 1.2 mg/h) attenuated the FBF response to MCh significantly (from 28.9+/-5.7 to 21.5+/-3.2 ml/min/100 ml tissue at 4 microg/min; p < 0.05), whereas both baseline FBF and the response to SNP were unchanged. In conclusion, this investigation showed that commonly used antihypertensive drugs affect endothelial vasodilator function in a different ways. ACE inhibition enhanced EDV, whereas a nonselective beta-blocker attenuated EDV. The calcium channel blocker, verapamil, improved both EDV and EIDV, probably by a direct effect on the vascular smooth-muscle cells.