Renoprotective effects of nitric oxide in angiotensin II-induced hypertension in the rat

Abstract

Experiments were performed in anesthetized male Sprague-Dawley rats to determine whether increased nitric oxide (NO) activity during the development of hypertension exerts a protective effect on renal cortical blood flow (CBF) and medullary blood flow (MBF). The effects of acute NO synthase inhibition on renal function and on CBF and MBF, measured by laser-Doppler flow probes, were evaluated in control and ANG II-infused hypertensive rats, prepared by the infusion of ANG II at a rate of 65 ng/min via osmotic minipumps implanted subcutaneously for 13 days. In normotensive rats ( n = 8), intravenous infusion of N ω-nitro-l-arginine (NLA; 20 μg ⋅ 100 g−1 ⋅ min−1) decreased CBF by 21 ± 4% and MBF by 49 ± 8% and increased blood pressure from 118 ± 1 to 140 ± 2 mmHg. In ANG II-infused rats ( n = 7), CBF and MBF decreased by 46 ± 5% and 25 ± 6%, respectively, during infusion of NLA. Arterial pressure increased from 160 ± 5 to 197 ± 7 mmHg, which was a greater absolute increase than in normotensive controls. Basal renal blood flow (RBF), estimated from p-aminohippurate clearance and hematocrit, was similar in both the control (6.0 ± 0.5 ml ⋅ min−1 ⋅ g−1) and hypertensive (6.0 ± 0.6 ml ⋅ min−1 ⋅ g−1) rats. However, NLA-induced reductions in RBF averaged 60 ± 5% in the hypertensive rats, compared with 31 ± 9% observed in control rats. GFR in control (0.97 ± 0.03 ml ⋅ min−1 ⋅ g−1) and hypertensive rats (0.78 ± 0.12 ml ⋅ min−1 ⋅ g−1) decreased to a similar extent during the first 30-min period of NLA infusion. GFR returned toward control levels in control rats; in contrast, GFR remained significantly decreased in the ANG II-infused rats (0.58 ± 0.11 ml ⋅ min−1 ⋅ g−1). Basal urinary sodium excretion (0.2 ± 0.08 μeq ⋅ min−1 ⋅ g−1), fractional excretion of sodium (0.3 ± 0.13%), and urine flow (4.9 ± 0.39 μl ⋅ min−1 ⋅ g−1) in hypertensive rats did not increase significantly after NLA treatment as occurred in normotensive controls. These data suggest that a compensatory increase in nitric oxide activity partially counteracts the vasoconstrictor influence of elevated ANG II levels to regulate renal hemodynamics and maintain cortical perfusion in the renal circulation.