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 that is dependent on nitric oxide (NO) in both conscious intact and ovariectomized female rats. Our first objective was to test whether the hormone, when administered to approximate serum concentrations found in midterm pregnant rats, induces renal vasodilation in males. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) increased significantly, on average, by 33 and 49% over baseline, respectively, after 5 days of recombinant human relaxin (rhRLX) administration to 12 conscious male rats by subcutaneous osmotic minipump. There were also significant decreases in hematocrit, plasma osmolality, and sodium concentration. Another objective was to determine whether endogenous endothelin (ET; via the endothelial ET(B) receptor) mediates the NO-dependent renal vasodilation produced by relaxin. rhRLX or vehicle was administered to conscious female rats (n = 9 and 8 rats, respectively). On the fifth day, baseline GFR and ERPF were both increased, on average, by 20-30% in the rats administered rhRLX (P < 0.05 vs. vehicle). Next, the specific ET(B)-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 significant 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) relaxin induces marked changes in the renal circulation and in osmoregulation regardless of gender and 2) relaxin-induced renal vasodilation and hyperfiltration are mediated by endothelin through the endothelial ET(B) receptor subtype and NO.
Danielson
L A
LA
Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA.
Kercher
L J
LJ
Conrad
K P
KP
D000818:Animals; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000196:embryology*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020318:Rats, Long-Evans; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012065:Relaxin / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D012727:Sex Characteristics; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D011994:Recombinant Proteins; C087120:RES 701-1; D012065:Relaxin