Effect of alcohol, neurohypophysectomy, and vasopressin antagonists on hemorrhage-induced bradycardia in the rat.
During initial stages of hemorrhage in the rat, cardiovascular compensation leads to a tachycardia (mean +/- SE, 5.2 +/- 0.7%; n = 23) that helps prevent a large fall in blood pressure. This compensatory phase is followed by a decompensatory phase in which mean arterial pressure and heart rate fall. A rise in arginine vasopressin (AVP) levels has been postulated as the cause of this hemorrhage-induced bradycardia (HIB). The object of the present study was to determine whether interference with AVP release by alcohol anesthesia or neurohypophysectomy or by blockade of AVP receptors in the plasma or cerebral spinal fluid could attenuate HIB. Male Wistar rats were anesthetized with pentobarbital, surgically prepared, and bled to maintain a blood pressure of 40-50 mm Hg. After hemorrhage, heart rate decreased 15 +/- 2% (n = 6) with alcohol anesthesia compared with 32 +/- 3% (n = 7) with pentobarbital. After neurohypophysectomy, however, HIB remained unchanged (-15 +/- 2%; n = 5) compared with sham-operated controls (-19 +/- 3%; n = 6). Peripheral administration of two nonselective V1/V2 antagonists and one V2 antagonist had no effect on HIB, whereas a V1 antagonist significantly attenuated the heart rate decrease (-15 +/- 4%; n = 6) compared with controls (-32 +/- 3%; n = 7). None of the AVP antagonists tested at one tenth the peripheral dose had any effect on HIB when administered into the lateral ventricle of the brain, although a mixed serotonin, dopamine, and catecholamine antagonist, spiperone, potentiated the response. It was concluded that although peripheral release of AVP may be partially involved in the heart rate response to hemorrhage, central AVP release and central AVP receptors were not involved in HIB.
Miller
J H
JH
Animal Physiology Research Unit, School of Biological Sciences, Victoria University, Wellington, New Zealand.
Grattan
D R
DR
Averill
R L
RL
D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004326:Drinking; D004562:Electrocardiography; D000431:Ethanol / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006470:Hemorrhage / Q000503:physiopathology*; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D010904:Pituitary Gland, Posterior / Q000502:physiology* / Q000601:surgery; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology; D017483:Receptors, Vasopressin; D013134:Spiperone / Q000494:pharmacology; D014667:Vasopressins / Q000037:antagonists & inhibitors*
D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; C070737:argipressin, beta mercapto(beta,beta)-cyclopentamethylenepropionic acid(1)-Ile(2,4)-Ala-NH2(9)-; D014667:Vasopressins; D001127:Arginine Vasopressin; D000431:Ethanol; D013134:Spiperone; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D010424:Pentobarbital