NITRIC-OXIDE INFLUENCES BLOOD-FLOW DISTRIBUTION IN RENOVASCULAR HYPERTENSION

Endothelium-derived nitric oxide contributes to the regulation of regi onal blood flow. Inhibition of endothelium-derived nitric oxide synthe sis increases blood pressure and vascular resistance. Using the substr ate antagonist N-omega-nitro-L-arginine-methyl ester to block endothel ium-derived nitric oxide synthesis, we tested the hypothesis that, in two-kidney, one clip renovascular hypertension, endothelium-derived ni tric oxide plays an increased role in maintaining blood flow to the no nclipped kidney and other visceral organs compared with normotensive c ontrols. This could be due to increased vascular shear stress, a prima ry stimulus for endothelium-derived nitric oxide synthesis, after the onset of hypertension. In hypertensive rats with mild renal artery ste nosis, basal renal blood flow normalized by kidney weight was similar in the nonclipped and clipped kidneys. Basal blood pressure of control s was 98+/-2 mm Hg compared with 145+/-3 mm Hg in the two-kidney, one clip hypertensive rats. N-omega-nitro-L-arginine-methyl ester increase d blood pressure by 20+/-2 and 43+/-3 mm Hg in control and hypertensiv e rats, respectively. Compared with normotensive controls, basal resis tance was higher in all organ beds in the hypertensive rats including brain, heart, intestine, and kidney. With the exception of the renal c irculation, the increase in vascular resistance after N-omega-nitro-L- arginine-methyl ester was greater in hypertensive rats compared with n ormotensive controls. In the hypertensive rats, N-omega-nitro-L-argini ne-methyl ester caused a similar increase in vascular resistance in bo th the nonclipped and clipped kidneys, and this was not different from normotensive controls. These results suggest that, in two-kidney, one clip hypertensive rats, as in normotensive rats, endothelium-derived nitric oxide synthesis plays an important role in regulating regional hemodynamics. In this model of hypertension, the endothelium is not dy sfunctional but is a critical component in the adaptation of local org an perfusion to increased blood pressure.