Mediators of the contraction-evoked skeletal muscle depressor
response in anesthetized rats.
Toney, Glenn M., and Steven W. Mifflin.
Department of Pharmacology, University of Texas, Health Science
Center at San Antonio, San Antonio, TX 78284-7764
APStracts 3:0128A, 1996.
Experiments were performed in artificially ventilated, pentobarbital
anesthetized (60 mg/kg i.p.) rats to examine possible mediators of
cardiovascular responses to skeletal muscle contraction. Rhythmic
contractions of the hindlimb triceps surae muscle were produced by
electrically stimulating (0.1 ms, 50 Hz) the tibial nerve (motor
threshold - 22.7 +/- 2.3 [mu]A; n=10) using a one second on, one
second off pattern. Using this 50% duty cycle for 10 seconds produced
rhythmic muscle contractions which showed no signs of fatigue.
Rhythmic stimulation evoked significant (p<0.05) reductions in
mean arterial pressure (MAP) and small decreases in heart rate (HR)
that were abolished by neuromuscular blockade (n=4) with gallamine
triethiodide (5 mg/kg/hr i.v.). In contrast, sustained (5-60 sec)
tetanic stimuli typically produced small (5-10 mmHg) pressor effects.
Mediators of the depressor effects of muscle contraction were
investigated by recording MAP and HR responses before and after: 1)
non-selective blockade of muscarinic cholinergic receptors with
atropine sulfate (2.0 mg/kg i.v.) (n=5). 2) inhibition of nitric
oxide synthase (NOS) with N_-Nitro-L-Arginine Methyl Ester (L-NAME)
(300 [mu]M/kg i.v.) (n=7). 3) non-selective [beta]-adrenoceptor
blockade with DL-propranolol hydrochloride (2.0 mg/kg i.v.) (n=10).
4) bilateral adrenalectomy (n=4). Results indicate that atropine
treatment was without effect on the muscle contraction-evoked
decreases in MAP and HR. L-NAME-induced NOS inhibition significantly
increased baseline MAP (112.2 +/- 2.2 to 137.1 +/- 4.6 mmHg), and
significantly reduced (p<0.05) contraction-evoked depressor
effects without altering HR responses. In a separate group (n=5), MAP
was elevated to a level equivalent to that produced by L-NAME using
phenylephrine (PE) (7-10 [mu]g/kg/hr i.v.) to determine if the
attenuated MAP response following L-NAME could be explained as an
indirect effect of increasing MAP. Under these conditions, the muscle
contraction-evoked decrease in MAP was reduced to a similar extent as
that produced by L-NAME treatment. Propranolol administration and
bilateral adrenalectomy significantly (p<0.05) reduced
contraction-evoked depressor responses from 13.4 +/- 1.3 to 6.3 +/-
3.1 mmHg and from 14.3 +/- 2.9 to 7.7 +/- 2.2 mmHg, respectively,
without effecting baseline MAP. Furthermore, both treatments produced
small, insignificant reductions in the duration of depressor
responses. Both adrenalectomy and propranolol produced mild
bradycardia, reducing HR by 17 +/- 3.9 and 39 +/- 4.6 bpm
(p<0.05), respectively, but neither treatment altered HR
responses to muscle contraction. These data indicate that
contraction-induced depressor responses in rats do not involve
significant muscarinic receptor activation. In contrast, evidence
supports a significant participation of [beta]-adrenoceptor-mediated
effects of adrenal catecholamines in the observed responses. Finally,
while inhibition of NO production was shown to attenuated depressor
responses to muscle contraction in the present study, our data raise
the possibility that the observed response-deficits could be due to
an indirect effect produced by the pressor actions of L-NAME.
Received 21 July 1995; accepted in final form 26 February 1996.
APS Manuscript Number A793-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96