Mechanisms underlying the cardiovascular responses to intrathecal vasopressin administration in rats.
Vasopressinergic pathways within the spinal cord have been implicated in the control of cardiovascular function. This study was undertaken to determine the mechanisms whereby intrathecally administered arginine vasopressin (AVP) increases blood pressure and heart rate in anesthetized rats. The cardiovascular responses to intrathecal AVP administration were significantly attenuated after intravenous administration of the ganglionic blocking agent, chlorisondamine chloride, as were the pressor responses following alpha-adrenergic receptor blockade with phentolamine and the heart rate responses following beta-receptor blockade with propranolol. Intrathecal administration of the V1 vasopressin receptor antagonist d(CH2)5Tyr(Me)AVP completely blocked the cardiovascular responses to intrathecal AVP injections, but did not significantly alter the responses to intrathecal substance P injections. There was no evidence for the involvement of the renin-angiotensin system in the pressor responses to intrathecal AVP, as (i) an angiotensin II receptor blocking agent, [Sar1, Val5, Ala8]angiotensin, failed to significantly alter the responses to intrathecal AVP, and (ii) plasma renin levels did not change following administration of the peptide. Intrathecal injections of [3H]AVP suggest that only small amounts of the peptide may cross into the plasma during the time in which the cardiovascular variables are changing. These data provide evidence that intrathecally administered AVP discretely activates the sympathetic outflow to the heart and vasculature, and confirm the neurally mediated nature of the response.
Neuroscience Research Group, University of Calgary, Alta., Canada.
C L
CL
Riphagen
Q J
QJ
Pittman
D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002714:Chlorisondamine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012084:Renin-Angiotensin System / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D001127:Arginine Vasopressin; D011433:Propranolol; D002714:Chlorisondamine; D010646:Phentolamine