RESUMEN
BACKGROUND: The haemodynamic effects of intravenous infusion of the non-selective nitric oxide synthase (NOS) L-omega monomethyl arginine (L-NMMA) have previously been characterized in humans. Its effect of reducing cardiac index (CI) is an important reason for the increase in mortality in patients with septic shock receiving L-NMMA in a pivotal outcome trial for this indication. The mechanism for the reduction in CI however, is uncertain. METHODS: In this study, we investigated the haemodynamic and arterial stiffness response to a bolus intravenous infusion of L-NMMA (3 mg kg(-1) over 5 min) in 26 healthy human volunteers to clarify the likely cause of L-NMMA induced negative inotropic and chronotropic effects. Digital photoplethysmography (MicroMedical Pulse Trace) was used to derive two measures of arterial stiffness: stiffness index, a measure of large arterial stiffness, and reflection index (RI), a measure of small- to medium-sized arterial stiffness. Haemodynamic measurements of systolic blood pressure, diastolic blood pressure, heart rate, systemic vascular resistance index (SVRI), stroke index and CI were made using a bioimpedance monitor (BioZ Cardiodynamics). RESULTS: We found that changes in CI during L-NMMA are closely related to changes in RI and SVRI. CONCLUSION: The negative inotropic effect of L-NMMA may be a result of an increase in coronary vascular resistance and a resultant decrease in myocardial perfusion. The reduction in CI may also result from a direct reduction of the normal positive inotropic effect of NO by L-NMMA which is closely correlated with its effects on SVRI.
Asunto(s)
Arterias/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , omega-N-Metilarginina/farmacología , Adulto , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Femenino , Humanos , Masculino , Óxido Nítrico Sintasa/farmacología , Análisis de Regresión , Adulto JovenRESUMEN
AIM: Angiotensin II type 2 (AT2) receptors are believed to become over-expressed in response to cardiovascular damage and to mediate beneficial effects (e.g. vasodilation). It is unknown whether AT2 receptors are functionally expressed in patients with insulin resistance (INSR). In this study, we investigated the role of the highly selective AT2 receptor antagonist, PD123319, on arterial stiffness and haemodynamic parameters in patients with INSR, compared with an age- and gender-matched control (N) group to determine whether there is functional expression of vascular AT2 receptors in patients with INSR. METHODS: We studied 10 subjects with INSR [mean age 28 +/- 5 years, body mass index (BMI) 30.4 +/- 5.4 kg/m(2), mean cholesterol level 4.7 +/- 0.7 mmol/l, mean homeostasis model assessment 2.78 +/- 0.84] and 10 age- and gender-matched normal subjects (mean age 27 +/- 7 years, BMI 23.6 +/- 2.5 kg/m(2), mean cholesterol level 3.9 +/- 0.6 mmol/l). All were normotensive, non-smokers and on no medications. Subjects received a 3-min infusion of PD123319 (10 microg/min). At the end of the infusion, arterial stiffness indices [stiffness index (SI) and reflective index (RI)] and haemodynamic parameters [cardiac index, systemic vascular resistance index (SVRI) and stroke index (ZI)] were measured. RESULTS: RI (mean % change: INSR 13.8 +/- 15.5%, N -0.2 +/- 4.6, p = 0.04) and SVRI (mean % change: INSR 13.5 +/- 9.7%, N -1.5 +/- 5.7, p = 0.005) increased significantly in response to PD123319 infusion in patients with INSR compared with controls. There were no significant changes in SI, systolic blood pressure, diastolic blood pressure and ZI. CONCLUSION: The results suggest the functional expression of AT2 receptors in small vessels that determine the inflection of the digital volume pulse wave in patients with INSR, possibly as an indicator of early vascular damage.
Asunto(s)
Arteriosclerosis/tratamiento farmacológico , Hemodinámica/efectos de los fármacos , Imidazoles/farmacología , Resistencia a la Insulina/fisiología , Piridinas/farmacología , Receptor de Angiotensina Tipo 2/metabolismo , Vasoconstrictores/farmacología , Adolescente , Adulto , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , FotopletismografíaRESUMEN
OBJECTIVE: The aim of this study was to determine whether dietary supplementation with isoflavones from red clover affected ambulatory blood pressure and forearm vascular endothelial function in postmenopausal type 2 diabetic women. DESIGN: Sixteen postmenopausal type 2 diabetics treated with diet or oral hypoglycaemic therapy completed a randomized double-blind crossover trial of dietary supplementation with isoflavones from red clover (approximately 50 mg/day) for 4 weeks compared to placebo. Twenty-four-hour ambulatory blood pressure recordings and forearm vascular responses to acetylcholine, nitroprusside and L-nitromonomethylarginine (L-NMMA) were measured at the end of each treatment period. RESULTS: Mean daytime systolic and diastolic blood pressures were significantly lower during isoflavone therapy compared to placebo (-8.0 +/- 3.4 and -4.3 +/- 1.9 mmHg respectively, p < 0.05). The increase in forearm vascular resistance following L-NMMA was significantly greater during isoflavone supplementation (20.9 +/- 6.5) than placebo (3.7 +/- 2.9 arbitrary units, p < 0.05), suggesting an improvement in basal endothelial function. Plasma lipoproteins, glycated haemoglobin and forearm vascular responses to acetylcholine and nitroprusside did not differ significantly between isoflavone and placebo therapy. CONCLUSION: Isoflavone supplementation from red clover may favourably influence blood pressure and endothelial function in postmenopausal type 2 diabetic women.