Infusions of pressor agents selectively attenuate depressor responses to ACh in anesthetized dogs.
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.
Nakahara
T
T
Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Ishii
K
K
Tanaka
Y
Y
Nakayama
K
K
D000109:Acetylcholine / Q000494:pharmacology*; D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000201:enzymology; D001794:Blood Pressure / Q000187:drug effects*; D002091:Butyrylcholinesterase / Q000097:blood / Q000378:metabolism; D018679:Cholinergic Agonists / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D018679:Cholinergic Agonists; D014665:Vasodilator Agents; D010656:Phenylephrine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D000109:Acetylcholine