AJP - Heart and Circulatory Physiology, Vol 271, Issue 1 273-H281, Copyright © 1996 by American Physiological Society

ARTICLES

Infusions of pressor agents selectively attenuate depressor responses to ACh in anesthetized dogs

T. Nakahara, K. Ishii, Y. Tanaka and K. Nakayama
Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Japan.

In dogs anesthetized with pentobarbital sodium (30 mg/kg iv), infusions of phenylephrine (PE; 1-3 micrograms.kg-1.min-1 iv for 30 min and longer) caused sustained elevations in blood pressure and suppressed depressor responses to acetylcholine (ACh; 1 microgram/kg iv) in a dose- and time-dependent manner. The dose-response curve for ACh (0.01-100 micrograms/kg iv)-induced depressor responses was shifted to the right by approximately 80-fold after an intravenous infusion of PE (3 micrograms.kg-1.min-1) for 120 min. Similar suppression was observed when infusions of methoxamine (5 micrograms.kg-1.min-1 iv), norepinephrine (3 micrograms.kg-1.min-1 iv under blockade of beta-adrenoceptors), or angiotensin II (0.3 micrograms.kg-1.min-1 iv) were carried out. However, in dogs treated with prazosin (1 mg/kg iv) or hydralazine (1 mg/kg iv) to prevent elevations in blood pressure over the baseline level, PE (3 micrograms.kg-1.min-1 iv) failed to attenuate depressor responses to ACh. The suppression observed after PE infusion was specific to ACh-induced depressor responses; i.e., no suppression was observed on the depressor responses to other drugs, such as histamine, sodium nitroprusside, carbachol, and methacholine. Furthermore, neostigmine (bolus injection of 30 microgram/kg iv followed by an infusion of 15 micrograms.kg-1.h-1 iv) greatly diminished the suppressive effect of PE. Except for a slight increase in acetylcholinesterase (AChE) activity in renal arterial segments, activities of both AChE and butyryl-cholinesterase in plasma, erythrocytes, and pulmonary and renal arterial segments were unchanged after PE infusion. These results suggest that prolonged elevation in blood pressure and/or vasoconstriction selectively attenuates depressor responses to ACh through accelerated degradation of this material.