Endothelium-derived constricting factor in renovascular hypertension

We have reported that in two-kidney, one clip hypertensive rats, renal perfusion is maintained by a balance between the vasodilator endothelium-derived nitric oxide and the vasoconstrictor angiotensin II. Others have suggested that endothelium-derived constricting factor, reported to be thromboxane A2 and/or endoperoxide, contributes to increased blood pressure in angiotensin II-dependent hypertension. We hypothesized that in angiotensin II-dependent two-kidney, one clip hypertension, endothelium-derived constricting factor contributes to vasoconstriction of the clipped kidney following nitric oxide synthesis inhibition. Using radioactive microspheres, we studied renal blood flow to the stenotic kidney of two-kidney, one clip hypertensive rats 4 weeks after clipping. The influence of nitric oxide on systemic and renal hemodynamics was evaluated by determining the response to nitric oxide synthesis inhibition using 10 mg/kg N omega-nitro-L-arginine methyl ester in these rats, which were either not treated (n = 8) or treated (n = 8) with 4 mg/kg of the constricting factor receptor antagonist BMS 180,291. Mean basal blood pressure in rats was 167 +/- 9 mm Hg (mean +/- SEM). N omega-Nitro-L-arginine methyl ester increased blood pressure by 35 +/- 7 mm Hg (P < .001). In the clipped kidney, N omega-nitro-L-arginine methyl ester decreased renal blood flow by 40% (from 4.5 +/- 0.9 to 2.7 +/- 0.6 mL.min-1.g kidney-1; P < .01) and increased renal vascular resistance by 100% (from 51.9 +/- 9.6 to 105.0 +/- 19.2 mm Hg.mL-1.min-1.g kidney-1; P < .005).(ABSTRACT TRUNCATED AT 250 WORDS)