Beneficial effect of serotonin 5-HT2-receptor antagonism on renal blood flow autoregulation in cyclosporin-treated rats

Renal brood flow (RBF) autoregulation reappears in postischemic rat kidneys during serotonin (5-HT2) antagonism. The aim of the present study was to a nalyze whether 5-HT2 antagonism can ameliorate impaired RBF autoregulation in rats treated with 20 mg/kg per d cyclosporin A during 10 d. Autoregulati on of RBF was assessed during stepwise lowering of renal perfusion pressure from 110 to 70 mmHg by gradual compression of the aorta. Autoregulation wa s lost in the cyclosporin A-treated rats. During administration of the 5-HT 2 antagonist ritanserin (0.6 mg/kg intravenous bolus, followed by 1.2 mg/kg per h intravenous infusion during 1 h), autoregulation acutely reappeared. Intrarenal bolus injections of a selective 5-HT2-agonist, 2,5 dimethoxy-4- iodoamphetamine hydrochloride, elicited a significantly stronger renal vaso contraction in cyclosporin A-treated rats than in control rats. This findin g was also observed with serotonin after nitric oxide-synthase blockade. Th ese results (1) show the importance of 5-HT2-receptor-mediated vasoconstric tion in the suppression of vasodilatory autoregulation of RBF in experiment al cyclosporin A-induced renal dysfunction and (2) demonstrate that the com plete loss of RBF autoregulatian is not due to damage of the vascular smoot h muscle cells.