Infusions of pressor agents selectively attenuate depressor
responses to acetylcholine in anesthetized dogs.
Nakahara, Tsutomu, Kunio Ishii, Yoshio Tanaka, and Koichi Nakayama.
Department of Pharmacology, School of Pharmaceutical Sciences
APStracts 3:0063H, 1996.
In dogs anesthetized with sodium pentobarbital (30 mg/kg, i.v.),
infusions of phenylephrine (Phe; 1-3 [mu]g/kg/min, i.v., for 30 min
and longer) caused sustained elevations in blood pressure and
suppressed depressor responses to acetylcholine (ACh; 1 [mu]g/kg,
i.v.) in a dose- and time-dependent manner. The dose-response curve
for ACh (0.01-100 [mu]g/kg, i.v.)-induced depressor responses was
shifted to the right by about 80-fold after an infusion of 3
[mu]g/kg/min, i.v., of Phe for 120 min. Similar suppression was
observed when infusions of methoxamine (5 [mu]g/kg/min, i.v.),
norepinephrine (3 [mu]g/kg/min, i.v., under blockade of [beta]
-adrenoceptors) or angiotensin II (0.3 [mu]g/kg/min, i.v.) were
carried out. However, in dogs treated with prazosin (1 mg/kg, i.v.)
or hydralazine (1 mg/kg, i.v.) to prevent elevations in blood
pressure over the baseline level, Phe (3 [mu]g/kg/min, i.v.) failed
to attenuate depressor responses to ACh. The suppression observed
after Phe 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 (a bolus injection at 30
[mu]g/kg, i.v., followed by an infusion at 15 [mu]g/kg/h, i.v.)
greatly diminished the suppressive effect of Phe. Except for a slight
increase in acetylcholinesterase activity in renal arterial segments,
activities of both acetylcholinesterase and butyrylcholinesterase in
plasma, erythrocytes and pulmonary and renal arterial segments were
unchanged after Phe 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.
Received 15 May 1995; accepted in final form 18 January 1996.
APS Manuscript Number H457-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96