M. Verbeke et al., Beneficial effect of serotonin 5-HT2-receptor antagonism on renal blood flow autoregulation in cyclosporin-treated rats, J AM S NEPH, 10(1), 1999, pp. 28-34
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.