gms | German Medical Science

Objective: Since endothelial function and in particular the activity of nitric oxide (NO) regulates vascular tone, we analysed the effects of an angiotensin II receptor blocker vs. an ACE-inhibitor on renal endothelial function in type 2 diabetes.

Methods: In a multicenter, prospective, double-blind, randomized, forced titration controlled clinical trial we enrolled 96 patients (age: 30-80 years) with type 2 diabetes, estimated glomerular filtration rate (GFR) > 80 ml/min, hypertension (größer gleich 130/80 mmHg or with antihypertensive therapy) and with normo- or microalbuminuria. After discontinuation of ACE-inhibitors or Angiotensin II receptor blockers, we determined renal plasma flow (RPF) and GFR [both by constant input clearance technique] 24-h urinary sodium and albumin excretion and renal basal NO activity (change of RPF to i. v. administration of L-NMMA 5 mg/kg over 45 minutes) (D RPF)) as a pharmacodynamic estimation of endothelial function. All measurements were repeated after patients had been treated with either ramipril 5/10 mg/d or telmisartan 40/80 mg/d for 9 weeks.

Results: Baseline clinical and resting hemodynamic parameters did not differ between the two groups. Basal NO activity as assessed by the renal vasoconstrictor effect of L-NMMA was improved by telmisartan (N = 45, D RPF: 72 ± 60 vs. 105 ± 65 ml/min; p < 0.001) and ramipril (N= 42, D RPF 60 ± 79 vs. 88 ± 60 ml/min; p = 0.018) from baseline to end of treatment, with no significant difference between the two groups (adjusted difference (mean±SE: 17 ± 14ml/min, p = 0.214).

At rest RPF increased with telmisartan (652 ± 181 vs. 696 ± 201 ml/min, p < 0.047), GFR remained unchanged, and filtration fraction (FF) decreased (22.0+5.1 vs. 20.6+4.9 %, p=0.020), but no significant changes were observed in RPF,GFR, and FF with ramipril.

Conclusions: Both telmisartan and ramipril led to an increased basal NO activity, but only with telmisartan the renal perfusion profile at rest improved. Our data suggest that renal endothelial function as an early target for preventing diabetic nephropathy can be improved by blockade of angiotensin II in patients with type 2 diabetes.