SUBTHRESHOLD STIMULATION OF A SEROTONIN 5-HT3 REFLEX ATTENUATES CARDIOVASCULAR REFLEXES

Volume-sensitive and chemosensitive cardiopulmonary reflexes modulate volume homeostasis via renal sympathetic nerve activity (RSNA). Blunti ng of volume-sensitive cardiopulmonary reflexes is associated with vol ume retention, e.g., in hypertension, whereas the role of chemosensiti ve cardiopulmonary reflexes is largely unknown. To elucidate the possi ble role of chemosensitive cardiopulmonary reflexes in control of volu me homeostasis, we investigated whether subthreshold stimulation of 5- HT3 receptors modulates the control of RSNA by volume-sensitive cardio pulmonary reflexes or the arterial baroreceptor reflex in rats. Phenyl biguanide (PBG) was infused intravenously to stimulate 5-HT3 receptor s. Higher doses of PBG lowered RSNA, but a dose of 6 mu g/min, given a s a background infusion throughout the experiment, did not change arte rial pressure, heart rate (HR), or RSNA. Ten minutes after beginning t he 6 mu g/min PBG infusion, a 15-min volume expansion (0.9% saline, 5 or 10% body weight) was started to stimulate volume-sensitive cardiopu lmonary reflexes. In separate experiments, 5-min ramp infusions of met hoxamine and nitroglycerin to stimulate the arterial baroreceptor refl ex (evaluated by a 4-parameter logistic regression) were performed 15 min after beginning the PBG background infusion (6 mu g/min). During P BG infusion, the RSNA responses to volume expansions were significantl y 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. contro l -52 +/- 5%, n = 7, P < 0.05). The 5-HT3 receptor antagonist odansetr on (GR-38032F) abolished these effects of PBG. The maximum HR gain of the arterial baroreceptor reflex was impaired but the arterial barorec eptor control of RSNA was unaffected by PBG background infusion. We co nclude that 5-HT3-serotonergic cardiopulmonary chemoreceptors blunt th e RSNA decrease to volume loading. This mechanism may facilitate volum e retention when cardiac serotonin is increased.