Objective: One of the earliest signs of vascular change is endothelial dysfunction, which is also known to provoke albuminuria and to predict cardiovascular prognosis. The aim of this study was to analyze the effects of renin-angiotensin system (RAS) blockade on renal endothelial function.
Research design and methods: In a multicenter, prospective, double-blind, forced-titration, randomized study, 96 patients with type 2 diabetes, hypertension, glomerular filtration rate >80 ml/min, and normo- or microalbuminuria were treated once daily with 40/80 mg telmisartan or 5/10 mg ramipril for 9 weeks.
Results: The mean +/- SE fall in renal plasma flow (RPF) in response to intravenous N(G)-monomethyl-L-arginine (L-NMMA), reflecting the magnitude of nitric oxide (NO) activity, increased with telmisartan from 71.9 +/- 9.0 ml/min before therapy to 105.2 +/- 9.7 ml/min at the end of treatment (P < 0.001). With ramipril, RPF response to L-NMMA increased from 60.1 +/- 12.2 to 87.8 +/- 9.2 ml/min (P = 0.018). The adjusted difference between treatments was -17.1 +/- 13.7 ml/min (P = 0.214). In accordance, telmisartan increased RPF at rest (i.e., without L-NMMA) from 652.0 +/- 27.0 to 696.1 +/- 31.0 ml/min (P = 0.047), whereas ramipril produced no significant changes in RPF. The more the basal NO activity improved, the greater was the vasodilatory effect on renal vasculature (r = 0.47, P < 0.001).
Conclusions: In patients with type 2 diabetes, telmisartan and ramipril both increased NO activity of the renal endothelium significantly, which in turn may support the preservation of cardiovascular and renal function.