RESUMEN
BACKGROUND: The effect on endothelium-dependent and independent vasodilation of 24-week treatment with a fixed-dose combination of perindopril/indapamide (2/0.625 mg, daily) and atenolol (50 mg, daily), was evaluated in 62 untreated essential hypertensive patients according a double-blind, parallel group, randomized study. METHODS: Brachial artery flow-mediated dilation (FMD), response to sublingual glyceril trinitrate (GTN, 25 microg) and to cold pressor test (CPT) were measured at baseline and after treatments at 12 and 24 weeks, as change in diameter from ultrasound scans by a computerized system. RESULTS: Blood pressure (BP) was (P < 0.001) reduced in both groups, but to a greater (P < 0.01) extent in the perindopril/indapamide group. After 24 weeks, FMD was significantly increased (P < 0.01) by perindopril/indapamide (from 5.0 +/- 2.1 to 6.0 +/- 1.7%) but not by atenolol (from 5.1 +/- 1.8 to 5.5 +/- 1.8%). Improvement in FMD was not statistically related to BP reduction. Response to GTN was also significantly (P < 0.05) increased by perindopril/indapamide (from 6.2 +/- 1.9 to 6.9 +/- 1.7%), but not by atenolol (from 6.1 +/- 2.8 to 6.6 +/- 2.6%). Improvement in GTN response was significantly (P < 0.05) related to BP reduction. Response to CPT was significantly increased (P < 0.001) by perindopril/indapamide after 12 and 24 weeks, whereas atenolol significantly (P < 0.05) improved it only after 24 weeks. CONCLUSIONS: Treatment with perindopril/indapamide improves endothelium-dependent vasodilation in comparison with atenolol. This improvement was observed without significant relations with BP changes, suggesting a pressure-independent effect. Improvement in endothelium-independent and sympathetic-associated vasodilation was also observed. These results suggests that long term therapy with a fixed-dose combination of perindopril/indapamide affords vascular protection in hypertensive patients.
Asunto(s)
Hipertensión/tratamiento farmacológico , Indapamida/administración & dosificación , Perindopril/administración & dosificación , Adulto , Antihipertensivos/administración & dosificación , Atenolol/uso terapéutico , Arteria Braquial/efectos de los fármacos , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nitroglicerina/farmacología , Vasodilatación/efectos de los fármacosRESUMEN
DESIGN AND PARTICIPANTS: A double-blind, crossover, randomized study was designed to evaluate the effect of 3-month treatment with a lower versus a higher antihypertensive dosage of ramipril (5 or 10 mg/day) on nitric oxide (NO)-dependent vasodilation in 46 untreated patients with essential hypertension. Radial artery flow-mediated dilation (FMD), before and after the intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA), to block NO synthase, and the response to sublingual glyceril trinitrate (GTN, 25 microg) were measured at baseline and after the two treatment periods as a change in artery diameter (computerized system from ultrasound scans). Plasma angiotensin II and oxidative stress markers were also assessed. RESULTS: FMD was significantly (P < 0.01) lower in hypertensive patients (4.6 +/- 1.8%) than in normotensive subjects (7.1 +/- 2.6%), whereas the response to GTN was similar. L-NMMA significantly (P < 0.001) inhibited FMD in normotensive but not in hypertensive subjects. Mean 24-h ambulatory blood pressure, plasma angiotensin II and oxidative stress marker levels were similarly reduced at the end of the two treatment periods. Both dosages of ramipril significantly (P < 0.001) increased FMD (5 mg: 5.9 +/- 2.1%; 10 mg: 6.3 +/- 2.4%) without modifying the response to GTN. However, compared with baseline (11 +/- 19%), the inhibiting effect of L-NMMA on FMD (NO-dependent FMD) was significantly (P < 0.01) greater with ramipril 10 mg (49 +/- 12%) than 5 mg per day (38 +/- 15%). The improvement in FMD and NO-dependent FMD was not related to changes in plasma levels of angiotensin II or markers of oxidative stress. CONCLUSION: Treatment with ramipril at a higher dosage induced a greater improvement in NO-dependent vasodilation compared with the lower antihypertensive dosage in hypertensive patients.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Hipertensión/tratamiento farmacológico , Óxido Nítrico/metabolismo , Arteria Radial/efectos de los fármacos , Ramipril/farmacología , Vasodilatación/efectos de los fármacos , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/sangre , Arteria Radial/diagnóstico por imagen , Ramipril/administración & dosificación , UltrasonografíaRESUMEN
BACKGROUND: Since it has been demonstrated that soy diet can improve endothelial function, in the present study we evaluated the effect of dietary substitution of 25 g of animal proteins with soy proteins on endothelial dysfunction in renal transplant patients. METHODS: In 20 renal transplant patients (55 +/- 11 years, serum creatinine 1.7 +/- 0.6 mg/dl), brachial artery flow mediated dilation (FMD) and endothelium-independent vasodilation (sublingual nitroglycerine, 25 microg) were measured at baseline, after 5 weeks of a soy diet and finally after 5 weeks of soy wash-out. Changes in plasma lipids, markers of oxidative stress (lipid peroxides, LOOH) and inflammation (C-reactive protein), isoflavones (genistein and daidzein), asymmetric dimethyl arginine (ADMA) and L-arginine were also evaluated. RESULTS: At baseline, patients showed a significantly lower FMD as compared with age-matched healthy subjects (3.2 +/- 1.8 vs 6.3 +/- 1.9, respectively; P < 0.001), while response to nitroglycerine was similar. After soy diet, actual protein intake was not changed, cholesterol and lipid peroxides were significantly reduced, and isoflavones were detectable in plasma. Soy diet was associated with a significant improvement in FMD (4.4 +/- 2.0; P = 0.003 vs baseline), while response to nitroglycerine was unchanged. Improvement in FMD was related to L-arginine/ADMA ratio changes, but no significant relation was found to changes in cholesterol, lipid peroxides or genistein and daidzein plasma concentrations. After 5 weeks of soy diet discontinuation, FMD (3.3 +/- 1.7%) returned to baseline values and isoflavones were no longer detectable in plasma. CONCLUSIONS: A soy protein diet for 5 weeks improves endothelial function in renal transplant patients. This effect seems to be strictly dependent on soy intake as it disappears after soy withdrawal and is mediated by an increase in the L-arginine/ADMA ratio, independently of change in lipid profile, oxidative stress or isoflavones.
Asunto(s)
Trasplante de Riñón/métodos , Proteínas de Soja/metabolismo , Enfermedades Vasculares/dietoterapia , Adulto , Anciano , Proteína C-Reactiva/metabolismo , Dieta , Endotelio Vascular/embriología , Endotelio Vascular/metabolismo , Femenino , Humanos , Enfermedades Renales/metabolismo , Peroxidación de Lípido , Masculino , Persona de Mediana Edad , Estrés OxidativoRESUMEN
Myocardial infarction with angiographically normal coronary arteries was recognized more than 30 years ago. Since then, various series of patients with such condition have been described, but the etiology and pathogenesis still remain a matter of debate. Evidence exists for a role of coronary vasospasm, thrombosis, embolization and inflammation, per se or combined, in determining the occurrence of myocardial infarction with angiographically normal coronary arteries. Endothelial dysfunction, possibly superimposed to non-angiographically evident atherosclerosis, may be an underlying common feature predisposing to the acute event. Additionally, myocarditis may explain some of these occurrences. Myocardial infarction with normal coronary arteries is therefore likely to be the result of multiple pathogenetic mechanisms. Although most reports emphasize the good prognosis of this condition, in general much better than myocardial infarction with coronary artery disease, prognosis is likely variable according to the underlying mechanism. This review summarizes current knowledge on this condition and examines areas of recent progress.
Asunto(s)
Angiografía Coronaria , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/diagnóstico , Vasos Coronarios , Infarto del Miocardio/etiología , Aneurisma Coronario/complicaciones , Aneurisma Coronario/diagnóstico , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico , Trombosis Coronaria/complicaciones , Trombosis Coronaria/diagnóstico , Vasoespasmo Coronario/complicaciones , Vasoespasmo Coronario/diagnóstico , Diagnóstico Diferencial , Humanos , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Miocarditis/complicaciones , Miocarditis/diagnóstico , Pronóstico , Trombofilia/complicaciones , Trombofilia/diagnóstico , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Izquierda/diagnósticoRESUMEN
To compare the effect of antihypertensive drugs on endothelium-dependent vasodilation in the peripheral conduit arteries of patients with essential hypertension, in a prospective, randomized, parallel group study, endothelial function was assessed in 168 hypertensive patients before and after 6-month treatment with randomly assigned nifedipine GITS (30 to 60 mg, n=28), amlodipine (5 to 10 mg, n=28), atenolol (50 to 100 mg, n=29), nebivolol (5 to 10 mg, n=28), telmisartan (80 to 160 mg, n=29), and perindopril (2 to 4 mg, n=28). If necessary, hydrochlorothiazide (25 mg) was added to each compound. We evaluated brachial artery flow-mediated, endothelium-dependent dilation (high-resolution ultrasound) compared with endothelium-independent response to glyceryl trinitrate (25 microg/s). Brachial artery diameter was measured by automatic computerized analysis. Forty healthy subjects were evaluated as a control group. Oxidative stress production was evaluated by measuring plasma malondialdehyde and plasma lipoperoxides; plasma antioxidant capacity was assessed as ferric-reducing antioxidant power. Hypertensive patients showed a significantly (P<0.01) lower flow-mediated dilation (5.2+/-1.9%) as compared with healthy control subjects (7.1+/-2.6%). Response to glyceryl trinitrate was similar in control subjects and patients. At baseline, blood pressure, diameter, flow-mediated dilation, and response to glyceryl trinitrate were similar in the different treatment groups. All treatments similarly reduced blood pressure, but only perindopril increased flow mediated dilation (from 5.1+/-2 to 6.4+/-2.4%; P<0.01) without modifying the response to glyceryl trinitrate. Perindopril but also telmisartan nifedipine and amlodipine reduced oxidative stress and increased plasma antioxidant capacity. In patients with essential hypertension, ACE inhibitors appear to be the only compounds able to improve conduit artery endothelium-dependent vasodilation.