CHOLESTEROL FEEDING DOES NOT ALTER RENAL HEMODYNAMIC-RESPONSE TO ACETYLCHOLINE AND ANGIOTENSIN-II IN RABBITS

Aortic ring studies have demonstrated a decrease in endothelium-depend ent relaxation or an enhanced response to vasoconstrictors in rabbits fed a high-cholesterol diet. Whether such abnormalities exist in the r enal circulation is unclear. The purpose of this study was to determin e functional renal responses to acetylcholine (ACh) or angiotensin II (ANG II) infusion in anesthetized rabbits after 8-10 wk of either a co ntrol diet (ACh, n = 6; ANG II, n = 6) or a 1% cholesterol diet (ACh, n = 7; ANG II, n = 7). Mean arterial pressure (MAP), renal blood flow (RBF), and glomerular lar filtration rate (GFR) were measured. Renal v ascular resistance (RVR) was calculated as MAP/RBF. For ANG II experim ents, captopril (15 mu g . kg(-1). min(-1)) was infused to suppress en dogenous ANG II production. After two control clearance periods, eithe r ACh (1 mu g . kg(-1). min(-1)) or ANG II (0.5 ng . kg(-1). min(-1)) was infused into the renal artery; RBF was allowed to stabilize before experimental clearances. RBF increased with ACh (control: 25 +/- 2 to 39 +/- 2 ml/min; cholesterol: 26 +/- 2 to 40 +/- 3 ml/min) and decrea sed with ANG II infusions (control: 40 +/- 4 to 25 +/- 3 ml/min; chole sterol: 36 +/- 3 to 24 +/- 2 ml/min). Nitrate/nitrite excretion also i ncreased with ACh infusion (control: 2.3 +/- 1.0 to 5.2 +/- 1.8 nmol . kg(-1). min(-1); cholesterol: 2.3 +/- 0.3 to 6.0 +/- 1.3 nmol . kg(-1 ). min(-1)). However, there were no significant differences between co ntrol and cholesterol groups in either response. GFR was unaltered dur ing ACh and ANG II infusions. MAP, RVR, and urinary sodium and potassi um excretion did not differ between groups in response to either drug. These results suggest that, despite significant hypercholesterolemia and large-vessel atherosclerosis, both nitric oxide-induced vasodilati on and endothelium-dependent modulation of ANG II vasoconstriction in the renal circulation are unaffected by cholesterol feeding.