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

Abstract

Renal blood flow (RBF) autoregulation reappears in postischemic rat kidneys during serotonin (5-HT2) antagonism. The aim of the present study was to analyze whether 5-HT2 antagonism can ameliorate impaired RBF autoregulation in rats treated with 20 mg/kg per d cyclosporin A during 10 d. Autoregulation of RBF was assessed during stepwise lowering of renal perfusion pressure from 110 to 70 mmHg by gradual compression of the aorta. Autoregulation was lost in the cyclosporin A-treated rats. During administration of the 5-HT2 antagonist titanserin (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 vasoconstriction in cyclosporin A-treated rats than in control rats. This finding was also observed with serotonin after nitric oxide-synthase blockade. These results (1) show the importance of 5- HT2-receptor-mediated vasoconstriction in the suppression of vasodilatory autoregulation of RBF in experimental cyclosporin A-induced renal dysfunction and (2) demonstrate that the complete loss of RBF autoregulation is not due to damage of the vascular smooth muscle cells.