Pressor and bradycardic effects of centrally administered relaxin in conscious rats.
The current study tested the hypothesis that centrally administered relaxin elevates arterial pressure in conscious rats and that this hypertensive effect is mediated, at least in part, by central or peripheral vasopressin. Injection of human relaxin (0.068 or 0.34 microgram in 200 nL artificial cerebrospinal fluid) into the right lateral ventricle of conscious, unrestrained Sprague-Dawley rats caused significant dose-related increases in arterial pressure and decreases in heart rat. The pressor and bradycardic responses to intracerebroventricular injections of relaxin were significantly blunted by pretreatment with either intracerebroventricular or intravenous injection of a vasopressin receptor (V1) antagonist, suggesting that the cardiovascular effects of central relaxin are mediated, at least in part, by V1 receptors in the brain and perhaps also by vasopressin released into the peripheral circulation. Neither intracerebroventricular injection of the vehicle alone nor intravenous injection of relaxin (0.34 microgram) altered arterial pressure or heart rate. In contrast to the above, intravenous injections of relaxin (40 micrograms/kg) elicited pressor and tachycardic responses that were not blunted by pretreatment with either intracerebroventricular or intravenous injection of the V1 receptor antagonist. Together, these data suggest that in the central nervous system relaxin contributes to the regulation of cardiovascular function and that the mechanisms for the cardiovascular effects of central and peripheral relaxin are distinct.
Yang
R H
RH
Department of Cardiovascular Research, Genentech, Inc., South San Francisco, California 94080, USA.
Bunting
S
S
Wyss
J M
JM
Berecek
K H
KH
Zhang
L
L
Jin
H
H
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012065:Relaxin / Q000008:administration & dosage / Q000494:pharmacology*; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000097:blood
D065092:Antidiuretic Hormone Receptor Antagonists; D014667:Vasopressins; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D012065:Relaxin