Cardiovascular responses to intrathecal vasopressin in conscious and anesthesized rats.
Increases in mean arterial pressure and heart rate have been documented after the intrathecal administration of [Arg8]vasopressin (AVP) in rats. Prior studies in our laboratories with conscious rats indicated that these cardiovascular changes were associated with a marked hindlimb sensorimotor dysfunction. In this study, which represents the first systematic comparison of the effects of intrathecal AVP in conscious and anesthesized rats, we demonstrate that in conscious male Sprague-Dawley rats 1) the motor dysfunction induced by intrathecal AVP is accompanied by a rise in mean arterial pressure that is significantly greater than that produced by an equal intravenous dose of AVP, and 2) both paralytic and pressor effects of intrathecal but not intravenous AVP are blocked by the intrathecal administration of the V1-receptor antagonist d(CH2)5[Tyr(Me)2]AVP (V1-ANT) but are not blocked by intravenous phenoxybenzamine, hexamethonium, or [Sar1, Thr8]angiotensin II, an angiotensin II antagonist. In contrast, in anesthesized rats the arterial pressor response to intrathecal AVP was blocked by intrathecal V1-ANT, intravenous hexamethonium, and intravenous phenoxybenzamine. Furthermore, conscious but not anesthesized rats exhibited a tachyphylaxis to intrathecal AVP. These results indicate that intrathecal AVP produces both the cardiovascular changes and the sensorimotor deficits through interactions with centrally located V1-receptors. In addition, sympathetic catecholaminergic mechanisms mediate the rise in mean arterial pressure produced by intrathecal AVP in anesthesized rats, but they do not in conscious rats.
Martinez-Arizala
A
A
Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, DC 20307.
Holaday
J W
JW
Long
J B
JB
D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D006584:Hexamethonium Compounds; D010643:Phenoxybenzamine; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-