AJP - Regulatory, Integrative and Comparative Physiology, Vol 271, Issue 6 1500-R1506, Copyright © 1996 by American Physiological Society

ARTICLES

Subthreshold stimulation of a serotonin 5-HT3 reflex attenuates cardiovascular reflexes

R. Veelken, K. F. Hilgers, T. Ditting, W. Fierlbeck, H. Geiger and R. E. Schmieder
Department of Internal Medicine, University of Erlangen-Nurnberg, Germany.

Volume-sensitive and chemosensitive 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 chemosensitive cardiopulmonary reflexes is largely unknown. To elucidate the possible role of chemosensitive cardiopulmonary reflexes in control of volume homeostasis, we investigated whether subthreshold stimulation of 5-HT3 receptors modulates the control of RSNA by volume-sensitive cardiopulmonary reflexes or the arterial baroreceptor reflex in rats. Phenyl biguanide (PBG) was infused intravenously to stimulate 5-HT3 receptors. Higher doses of PBG lowered RSNA, but a dose of 6 micrograms/min, given as a background infusion throughout the experiment, did not change arterial pressure, heart rate (HR), or RSNA. Ten minutes after beginning the 6 micrograms/min PBG infusion, a 15-min volume expansion (0.9% saline, 5 or 10% body weight) was started to stimulate volume-sensitive cardiopulmonary reflexes. In separate experiments, 5-min ramp infusions of methoxamine and nitroglycerin to stimulate the arterial baroreceptor reflex (evaluated by a 4-parameter logistic regression) were performed 15 min after beginning the PBG background infusion (6 micrograms/min). During PBG infusion, the RSNA responses to volume expansions were significantly impaired (5% body weight: PBG -6 +/- 6%, n = 7 vs. control -39 +/- 9%, n = 6, P < 0.001; 10% body weight: PBG -33 +/- 6%, n = 8 vs. control -52 +/- 5%, n = 7, P < 0.05). The 5-HT3 receptor antagonist odansetron (GR-38032F) abolished these effects of PBG. The maximum HR gain of the arterial baroreceptor reflex was impaired but the arterial baroreceptor control of RSNA was unaffected by PBG background infusion. We conclude that 5-HT3-serotonergic cardiopulmonary chemoreceptors blunt the RSNA decrease to volume loading. This mechanism may facilitate volume retention when cardiac serotonin is increased.

This article has been cited by other articles:

				T. Ditting, K. F. Hilgers, K. E. Scrogin, A. Stetter, P. Linz, and R. Veelken Mechanosensitive cardiac C-fiber response to changes in left ventricular filling, coronary perfusion pressure, hemorrhage, and volume expansion in rats Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H541 - H552. [Abstract] [Full Text] [PDF]

				P. Linz and R. Veelken Serotonin 5-HT3 receptors on mechanosensitive neurons with cardiac afferents Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1828 - H1835. [Abstract] [Full Text] [PDF]

				D. C. Merrill, J. L. Segar, O. J. McWeeny, and J. E. Robillard Sympathetic responses to cardiopulmonary vagal afferent stimulation during development Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1311 - H1316. [Abstract] [Full Text] [PDF]

				V. L. L. Oliveira, E. D. Moreira, V. d. M. A. Farah, F. Consolim-Colombo, E. M. Krieger, and M. C. Irigoyen Cardiopulmonary Reflex Impairment in Experimental Diabetes in Rats Hypertension, October 1, 1999; 34(4): 813 - 817. [Abstract] [Full Text] [PDF]

				T. J. Scislo, R. A. Augustyniak, and D. S. O'Leary Differential arterial baroreflex regulation of renal, lumbar, and adrenal sympathetic nerve activity in the rat Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1998; 275(4): R995 - R1002. [Abstract] [Full Text] [PDF]