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

Abstract

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.