Effect of ACE inhibition and angiotensin AT1 receptor blockade on renal and blood pressure response to L-arginine in humans

Objective Nitric oxide (NO) may contribute to the actions of angiotensin co nverting enzyme (ACE) inhibitors. In contrast, angiotensin type 1 (AT1) rec eptor blockers (AT1B) have been considered to act exclusively by inhibiting angiotensin II actions. However, recent experimental findings suggest that AT1B actions may be also partly mediated by NO. In this study, we explored whether ACE inhibitors and AT1B modulate hemodynamic responses to L-argini ne (L-arg), a NO precursor. Methods Systemic (Finapres) and renal hemodynamic responses to L-arg (200 m g/kg body weight), associated with markers of systemic and renal NO product ion, were assessed before (control) and after 3 weeks of randomized pretrea tment with the ACE inhibitor ramipril (5 mg/day for 3 weeks) or the AT1B lo sartan (50 mg/day for 3 weeks) in nine healthy male subjects (33 +/- 2 year s; body mass index 25.5 +/- 0.5 kg/m(2)). Results Control L-arg did not influence mean arterial pressure (MAP) (92 +/ - 5 versus 90 +/- 5 mmHg; not significant). In contrast, L-arg decreased MA P when administered after pretreatment with ramipril (89 +/- 5 versus 83 +/ - 4 mmHg; P < 0.01) or losartan (90 +/- 44 versus 86 +/- 4; P < 0.05). Cont rol L-arg infusion had no effect on renal plasma flow (RPF) (paraminohippur ic acid clearance) and renal vascular resistance (RVR), whereas the glomeru lar filtration rate (GFR) (inulin clearance) decreased (98 +/- 4 versus 89 +/- 5 ml/min; P < 0.05), resulting in a decrease in filtration fraction (P < 0.05). After ramipril, L-arg induced renal vasodilation as indicated by s ignificant changes in RPF (576 +/- 41 versus 669 +/- 21 ml/min; P < 0.01) a nd RVR (P < 0.05). The GFR did not change statistically after ramipril pret reatment (91 +/- 3 versus 97 +/- 4 ml/min; not significant); however, the t rend was different as compared with control (F = 5.7, P < 0.05). L-Arg-indu ced renal vasodilation was also observed after losartan (RPF, 637 +/- 34 ve rsus 706 +/- 40 ml/min; P < 0.05). Enhanced renal and systemic responses to L-arg after ACE inhibitor and AT1B were associated with a rise in plasma L -citrulline levels, which was greater than after control L-arg (P< 0.05). H owever, other indicators of NO activity such as plasma and urinary cyclic g uanosine 3',5'-monophosphate, and nitrates, remained unchanged throughout a ll experiments. Conclusion The results indicate that ACE inhibitors and AT1B have a potenti al to enhance L-arg-induced vasodilation both in systemic and renal vascula r beds. However, these hemodynamic responses were not associated with convi ncing changes in indicators of systemic or renal NO activity, suggesting a contribution of NO-independent vasodilator mechanisms. J Hypertens 2000, 18 :51 - 59 (C) Lippincott Williams & Wilkins.