Impact of gender and endothelin on renal vasodilation and hyperfiltration induced by relaxin in conscious rats

Chronic administration of the hormone relaxin elicits renal vasodilation th at is dependent on nitric oxide (NO) in both conscious intact and ovariecto mized female rats. Our first objective was to test whether the hormone, whe n administered to approximate serum concentrations found in midterm pregnan t rats, induces renal vasodilation in males. Glomerular filtration rate (GF R) and effective renal plasma flow (ERPF) increased significantly, on avera ge, by 33 and 49% over baseline, respectively, after 5 days of recombinant human relaxin (rhRLX) administration to 12 conscious male rats by subcutane ous osmotic minipump. There were also significant decreases in hematocrit, plasma osmolality, and sodium concentration. Another objective was to deter mine whether endogenous endothelin (ET; via the endothelial ETB receptor) m ediates the NO-dependent renal vasodilation produced by relaxin. rhRLX or v ehicle was administered to conscious female rats (n = 9 and 8 rats, respect ively). On the fifth day, baseline GFR and ERPF were both increased, on ave rage, by 20-30% in the rats administered rhRLX (P < 0.05 vs. vehicle). Next , the specific ETB-receptor antagonist RES-701-1 was infused intravenously over 4 h in both groups of rats. In response to RES-701-1, there was a sign ificant decline in both GFR and ERPF in the rats receiving rhRLX such that renal function converged in the two groups of animals. We conclude 1) relax in induces marked changes in the renal circulation and in osmoregulation re gardless of gender and 2) relaxin-induced renal vasodilation and hyperfiltr ation are mediated by endothelin through the endothelial ETB receptor subty pe and NO.