Effects of vasodilatory antihypertensive agents on endothelial dysfunctionin rats with ischemic acute renal failure

Ischemic acute renal failure is associated with vascular endothelial dysfun ction. We examined whether vasodilatory antihypertensive agents would impro ve endothelial function in rats with ischemia/reperfusion renal injury. Rat kidneys were isolated and perfused after clipping of the bilateral renal a rteries for 45 min and reperfusion for 24 h, and renal perfusion pressure a nd nitric oxide concentration in the venous effluent (chemiluminescence ass ay) were monitored, Preischemic administration of celiprolol (a beta-blocke r; 100 mg/kg p.o.), benidipine (a calcium channel blocker; 1 mg/kg p.o.), o r imidapril (an angiotensin converting-enzyme inhibitor; 3 mg/kg p.o,) rest ored endothelial function in rats subjected to acute renal ischemia (Delta renal perfusion pressure [10(-8) M acetylcholine]: sham -42+/-3%, ischemia -31+/-1%, ischemia +celiprolol -39+/-1%*, ischemia+benidipine -38+/-2%*, is chemia+imidapril -42+/-2%*; *p<0.05 vs, ischemia), Serum urea nitrogen and creatinine levels were also lower in the treated groups, Furthermore, ische mia-induced decreases in the response to acetylcholine and renal excretory function were smaller in SHR than in deoxycorticosterone-salt hypertensive rats, in which endothelial damage was marked. These results suggest that pr eischemic endothelial function may influence the degree of ischemic renal i njury. Calcium channel blockers, converting enzyme inhibitors, and endothel ial NO synthase-activating beta-blockers had beneficial effects on renovasc ular endothelial dysfunction due to ischemia.