Nitric oxide modulates the development and surgical reversal of renovascular hypertension in rats

Objective To evaluate the role of nitric oxide (NO) in the development and unclipping-induced reversal of blood pressure and bilateral renal function in two-kidney, one clip (2K1C) Goldblatt hypertensive rats. Methods Goldblatt hypertensive rats were prepared by clipping the left rena l artery 4 weeks before unclipping experiments. NG-nitro-L-arginine methyl ester (L-NAME) was administered after clipping and during unclipping to inh ibit nitric oxide (NO) synthesis. Blood pressure and bilateral renal respon ses were measured. Results Chronic L-NAME treatment accelerated and aggravated blood pressure elevations and increased plasma nitrite and nitrate levels in 2K1C rats. Su rgical removal of the renal artery clip induced profound reductions in bloo d pressure in rats with and without L-NAME treatment. However, the magnitud e of the unclipping-induced depressor response at the first post-unclipping hour was significantly smaller in L-NAME-treated rats compared to those wi thout L-NAME administration (15 +/- 1 versus 22 +/- 1%, P< 0.05). Two hours after unclipping, blood pressure of both groups fell to a comparable, norm al level. Acute intravenous infusion of L-NAME in established 2K1C hyperten sive rats further increased blood pressure. Subsequent unclipping caused a depressor response similar to that observed in hypertensive rats treated ch ronically with L-NAME. Despite the marked decreases in blood pressure, uncl ipping induced striking increases in glomerular filtration rate (GFR), urin e flow and sodium and potassium excretion rates in the ipsilateral kidney. However, the magnitudes of increases in GFR and the diuretic and natriureti c responses in rats without L-NAME treatment were significantly greater tha n in rats with L-NAME administration. In contrast, unclipping reduced these function indices in the contralateral kidney to a similar level in rats wi th and without L-NAME treatment. Conclusions NO exerts vasodilator action and thereby lessens renal artery c lipping-induced blood pressure elevation. Furthermore, unclipping-induced r elease of NO partially contributes to the early reduction in blood pressure and changes in bilateral renal function but does not directly mediate the normalization of blood pressure after unclipping in this hypertension model . I Hypertens 2000, 18:601-613 (C) Lippincott Williams & Wilkins.