Subthreshold stimulation of a serotonin 5-ht3 reflex attenuates
cardiovascular reflexes.
Veelken, Roland, Karl F. Hilgers, Till Ditting, Wolfgang Fierlbeck,
Helmut Geiger, and Roland E. Schmieder.
Department of Internal Medicine, University of Erlangen
-N[umlaut]urnberg, Germany
APStracts 3:0242R, 1996.
Volume-sensitive and chemo-sensitive cardiopulmonary reflexes modulate
volume homeostasis via renal sympathetic nerve activity (RSNA) .
Blunting of volume-sensitive cardiopulmonary reflexes is associated
with volume retention e.g. in hypertension, whereas the role of
chemo-sensitive cardiopulmonary reflexes is largely unknown. To
elucidate the possible role of chemo-sensitive cardiopulmonary
reflexes in control of volume homeostasis, we investigated whether
subthreshold stimulation of 5HT3 receptors modulates the control of
RSNA by volume-sensitive cardiopulmonary reflexes or the arterial
baroreceptor reflex in rats. Phenylbiguanide (PBG) was infused iv to
stimulate 5HT3 receptors. Higher doses of PBG lowered RSNA, but a
dose of 6 [mu]g/min, given as a background infusion throughout the
experiment, did not change arterial pressure, heart rate or RSNA. Ten
min after beginning the 6 [mu]g/min PBG infusion, a 15 min volume
expansion (0.9% saline, 5 or 10 % of body weight) was started to
stimulate volume-sensitive cardiopulmonary reflexes. In separate
experiments, 5 min ramp infusions of methoxamine and nitroglycerine
to stimulate the arterial baroreceptor reflex (evaluated by a 4
-parameter logistic regression) were performed 15 min after beginning
the PBG background infusion (6[mu]g/min). During PBG infusion, the
RSNA responses to volume expansions were significantly impaired (5%
body weight - PBG: -6+/-6% (n=7) versus control -39+/-9% (n=6)
p<0.001; 10% body weight - PBG: -33+/-6% (n=8) versus control
-52+/-5% (n=7) p<0.05 ). The 5HT3 receptor antagonist odansetron
abolished these effects of PBG. The maximum heart rate gain of the
arterial baroreceptor reflex was impaired but the arterial
baroreceptor control of RSNA was unaffected by PBG background
infusion. We conclude that 5HT3-serotonergic cardiopulmonary
chemoreceptors blunt the renal sympathetic nerve activity decrease to
volume loading. This mechanism may facilitate volume retention when
cardiac serotonin is increased.
Received 27 February 1996; accepted in final form 20 May 1996.
APS Manuscript Number R117-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96