Linz, Peter, and Roland Veelken. Serotonin 5-HT3 receptors on mechanosensitive neurons with cardiac afferents. Am J Physiol Heart Circ Physiol 282: H1828-H1835, 2002; 10.1152/ajpheart.00708.2000.-In rats, the mechanosensitive cardiorenal baroreflex influencing renal excretory function might be impaired by serotonin occurring in coronary arteries, e.g., in hypertension. Because the afferent limb of this reflex could be affected, we investigated the responses of nodose ganglion cells (one neuron of reflex) to osmotic, mechanical stress in presence or absence of the serotonin 5-HT3 receptor agonist phenylbiguanide (PBG). Current-voltage relationships (from Ϫ100 to ϩ50 mV) were obtained using cell patch recordings while the cells were exposed to control or hypoosmotic solutions to induce mechanical stress. This protocol was repeated after low doses of PBG (10 M), angiotensin II (10 nM), or the stretch-activated channel blocker gadolinium (20 M) were added to the extracellular medium (EM). Hypoosmotic EM induced significant changes in cellular conductance. The full-range current-voltage relationship allowed for the calculation of a mean reversal potential of Ϫ13 Ϯ 1.2 mV with respect to this change in cellular conductance (n ϭ 44). This increase in conductance was impaired after addition of either PBG or gadolinium to the EM,which was statistically evaluated at a voltage of Ϫ80 mV, where influences of voltage-gated channels are not likely to interfere with the responses recorded. The serotonin 5-HT 3 receptor antagonist tropisetron (10 nM) prevented the PBG effect on conductance responses. Angiotensin II had no influence. Hence, serotonin might decrease the mechanical sensitivity of afferent cardiac nerves controlling renal sympathetic nerve activity. mechanosensitivity; renal innervation THE SYMPATHETIC NERVOUS SYSTEM influences the circulation not only by its effect on the regulation of peripheral resistance or cardiac performance, but also by controlling volume homeostasis via efferent renal sympathetic nerve activity (RSNA) (4, 28). Thus an impairment of RSNA regulation is likely to contribute to the development of volume overload in various pathophysiological situations, like in hypertension (13), but also in sodium-retaining disorders, like congestive heart failure (5, 11, 11). The activity of renal sympathetic nerve fibers is very specifically controlled by cardiopulmonary reflexes (28, 31) whose afferent branch is contained within the vagus nerve. Cardiopulmonary reflexes are not only stimulated by changes in cardiac filling pressure, but also by chemical agents (17). Endogenous substances stimulating these reflexes are prostaglandins and serotonin, by serotonin 5-HT 3 receptors. In previous experiments (31), we could demonstrate that the control of RNSA by mechanosensitive cardiopulmonary reflexes stimulated with a saline volume load was considerably impaired in rats preinfused with subthreshold doses of the serotonin 5-HT 3 receptor agonist phenylbiguanide (PBG). The impaired response could be restored aft...