Effects of cardiovascular angiotensin II type 1 receptor blockade on nitric oxide synthase inhibition in patients with insulin resistance syndrome.
BACKGROUND
There is evidence that in the early stages of type II diabetes, the cardiovascular system compensates by increasing endothelial nitric oxide synthase (e-NOS) expression. In the advanced stages of disease, e-NOS is diminished, and is associated with endothelial dysfunction. Angiotensin II, acting via the angiotensin II type 1 (AT(1)) receptor, is central to the development of endothelial dysfunction. The effect of AT(1) receptor blockade on NOS expression and activity in humans with early insulin resistance syndrome (INSR) has not been previously investigated. Eight subjects with INSR participated in a randomized, double-blind, placebo-controlled, crossover study. Subjects were randomized to receive telmisartan or placebo (1 month of each) in a two-period crossover study with a 1-week washout period in between. The arterial stiffness and haemodynamic response to intravenous L-nitro-monomethyl arginine (L-NMMA 3mg/kg) was assessed at baseline and at the end of each treatment phase. SI (Stiffness index, a measure of large artery stiffness) and RI (Reflection index, small- to medium-sized arterial stiffness) were measured using digital photoplethysmography. Haemodynamic parameters [Heart rate (HR), Systolic blood pressure (SBP), Diastolic BP (DBP) and systemic vascular resistance index (SVRI)] were measured non-invasively using trans-thoracic bioimpedance.


RESULTS
Telmisartan significantly reduced baseline SI, SBP, DBP and SVRI. Infusion of L-NMMA produced a significant increase in RI and a significant reduction in HR during placebo therapy. Telmisartan therapy attenuated these responses.


CONCLUSIONS
Telmisartan therapy reduced NOS activity and/or expression in these subjects, possibly because of improved vascular function arising from AT(1) receptor blockade.
Brillante
Divina Gracilla
DG
Department of Medicine, St. George Clinical School, University of New South Wales, Level 2 WR Pitney Building, Chapel Street, Kogarah, NSW, Australia.
O'Sullivan
Anthony John
AJ
Brillante
Ruby Esmeralda
RE
Howes
Laurence Guy
LG
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D001562:Benzimidazoles; D001565:Benzoates; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017156:Photoplethysmography; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D000077333:Telmisartan; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology
D001562:Benzimidazoles; D001565:Benzoates; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D000077333:Telmisartan