Reflex inhibition of efferent renal sympathetic nerve activity by 5-hydroxytryptamine and nicotine is elicited by different epicardial receptors

Abstract

Intrapericardial administration of 5-hydroxytryptamine (5-HT) induced reflex effects consisting in an inhibition of renal sympathetic nerve activity (RSNA), bradycardia and a fall in blood pressure. Nicotine caused the same reflex effects as 5-HT. The reflex effects of both 5-HT and nicotine were abolished by vagotomy. MDL 72222, an antagonist at 5-HT M-receptors, abolished or attenuated the decreases in RSNA, heart rate and blood pressure induced by 5-HT, leaving the reflex effects of nicotine unchanged. In the absence of MDL 72222 the reflex bradycardia partially concealed a positive chronotropic response to 5-HT. After blockade of the bradycardia response by MDL 72222, 5-HT elicited a significant tachycardia, which was not altered by propranolol and phentolamine, but was prevented by phenoxybenzamine. 5-HT probably reaches the sinoatrial node and activates 5-HT receptors that mediate directly the increase in heart rate. The nicotine receptor antagonist hexamethonium selectively abolished or attenuated the reflex effects of nicotine without interfering with those of 5-HT. We conclude that 5-HT and nicotine elicit similar reflex effects in epicardial vagal nerve endings by stimulation of M-receptors or nicotine receptors, respectively.

The thromboxane A2 mimetic U-46619 inhibits somatomotor activity via a vagal reflex from the lung

“…The absence of a depressor response after intrapericardial U-46619 injection suggests that thromboxane A 2 is not an endogenous chemical capable of evoking the coronary chemoreflex. Previous studies demonstrate that intravenous U-46619 evokes a breathing pattern (22,31,32) similar to the vagally mediated pulmonary respiratory chemoreflex (9, 10), and many chemicals, including serotonin, phenyl biguanide, and nicotine, that evoke the pulmonary respiratory chemoreflex also evoke the pulmonary depressor chemoreflex and coronary chemoreflex (10,25,33,35). Thus it seemed reasonable to expect that intravenous and intrapericardial U-46619 would evoke a reflex hypotension.…”

“…The absence of a depressor response after intravenous U-46619 in the present study and in previous studies (4,22) might be due to U-46619's direct vasoconstrictor effect (31,32) overriding the pulmonary depressor chemoreflex. Although a distinction has been made between the coronary chemoreflex [evoked by chemical injection into the coronary arteries (10)] and the epicardial chemoreflex [evoked by chemical injection into the pericardial sac (33)], the same chemicals often evoke both of these reflexes (10,25,33,35). However, in the rabbit for example, intravascular but not intrapericardial phenyl biguanide injection elicits a depressor reflex from the heart (1).…”

Roles for CCK1 and 5‐HT3 receptors in the effects of CCK on presympathetic vasomotor neuronal discharge in the rat

“…Firstly, we have previously shown that the actions of CCK on arterial blood pressure and splanchnic sympathetic nerve discharge are dependent on intact vagal afferents (Sartor & Verberne, 2002). Similarly, the sympathoinhibitory effects of PBG are sensitive to vagal section (Mohr et al ., 1987; Evans et al ., 1990). Secondly, CCK 1 receptors and 5‐HT 3 receptors are found on the cell bodies of vagal afferents and are transported to peripheral sites by axonal transport mechanisms (Zarbin et al ., 1981; Kilpatrick et al ., 1990; Lin & Miller, 1992; Corp et al ., 1993; Uneyama et al ., 2002).…”

Production and Function of Serotonin in Cardiac Cells

“…Initially, 5-HT 3 -receptors seemed only to be present in nerve cells in the heart and might mediate the "von Bezold-Jarisch" reflex [97]. The 5-HT 3 -receptors seem to be found in epicardial afferent sensory nerve ending of the vagus [160]. More recently, however, using a new knockout mouse, 5-HT 3 -receptors were found at least in the ventricle of wild-type mice [110].…”