Cyclosporine-induced hypotension.
The cardiovascular effects of i.v. infusion of cyclosporine were studied in pentobarbital-anesthetized rabbits. In doses ranging from 0.5 to 120 mg/kg/hr, CsA induced significant, sustained, dose-dependent hypotension. At the 60 mg/kg/hr dose the average drop in diastolic blood pressure was 27 mmHg (n = 9). Possible mechanisms were investigated by comparison of heart rate and blood pressure responses to physiologic manipulation, metabolic inhibition, or receptor antagonism before and after infusion of CsA. CsA did not modify responses to vagal stimulation, decreases in heart rate and blood pressure, P less than 0.001 and P less than 0.002, respectively. However, the cardiovascular reflex response during recovery was significantly attenuated after CsA infusion, P less than 0.05, n = 7. Response to bilateral carotid occlusion after CsA was decreased by 17 mmHg (n = 8, P less than 0.01). There were no significant differences between CsA alone and CsA plus glycopyrrolate or CsA plus aspirin. In this cyclosporine-induced hypotensive rabbit model, the hypotensive response appears to be related to a decrease in the endogenous sympathetic adrenergic activity, not to alterations in cholinergic tone, ganglionic transmission, or vasodilatory prostaglandin metabolism.
Parkhurst
G W
GW
Department of Pharmacology, Rush Medical College, Chicago, Illinois 60612.
Moon
B H
BH
Xia
R L
RL
Littleton
M T
MT
Prancan
A V
AV
D000320:Adrenergic Fibers / Q000502:physiology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D003524:Cyclosporins / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006024:Glycopyrrolate / Q000494:pharmacology; D007022:Hypotension / Q000139:chemically induced*; D007262:Infusions, Intravenous; D011817:Rabbits; D014630:Vagus Nerve / Q000502:physiology
D003524:Cyclosporins; D001241:Aspirin; D006024:Glycopyrrolate