Role of nucleus tractus solitarius (NTS) 5-HT3 receptors in the defense reaction-induced inhibition of the aortic baroreflex in rats

CBaR: cardiac baroreflex response CPBG: 1-(m-chlorophenyl)-biguanide DMH: dorsomedial nucleus of the hypothalamus dPAG: dorsal part of the periaqueductal gray ECG: electrocardiogram HR: heart rate MBP: mean blood pressure NTS: nucleus tractus solitarius SBaR: sympathetic baroreflex response 3 ABSTRACT Different stressful conditions elicit a typical behaviour called the defense reaction. Our aim was to determine whether 5-HT 3 receptors in the nucleus tractus solitarius (NTS) are involved in (i) the inhibition of the baroreflex bradycardia and (ii) the rise in blood pressure which are known to occur during the defense reaction. In urethane-anesthetized rats, the defense reaction was elicited by electrical stimulation of the dorsomedial nucleus of the hypothalamus (DMH) or the dorsal part of the periaqueductal gray (dPAG). Direct electrical stimulation of the aortic depressor nerve was used to trigger the typical baroreflex responses. Aortic stimulation at high (100-150 µA) and low (50-90 µA) intensity produced a decrease in heart rate of-39 to-44 % (relative to baseline, Group 1 responses, n=113) and-19 % to-24 % (Group 2 responses, n=43), respectively. In spontaneously breathing rats, Group 1 and Group 2 bradycardiac responses were inhibited during DMH (-75 ±4% and-96 ±4%, n=38 and n=11, respectively), as well as dPAG (-81±3 % and-95±4 %, n=36 and n=10, respectively) stimulation. The aortic baroreflex bradycardia was hardly affected by DMH or dPAG stimulation when bicuculline (5 pmol), a specific GABA A receptor antagonist, had previously been microinjected into the NTS. Likewise, NTS microinjections of granisetron, a specific 5-HT 3 receptor antagonist, prevented, in a dose-dependent manner, the baroreflex bradycardia inhibition. In addition, intra-NTS granisetron did not affect the rise in blood pressure induced by either site stimulation. These data show that 5-HT 3 receptors in the NTS are involved in the GABAergic inhibition of the aortic baroreflex bradycardia, but not in the rise in blood pressure, occurring during the defense reaction elicited by DMH or dPAG stimulation.