Effects of central histaminergic receptor activation on carotid sinus baroreceptor reflex resetting in stressed rats / 生理学报

To determine the effect of stress on carotid sinus baroreceptor reflex (CSR) and whether or not central histaminergic receptors modulate the CSR under stress, the characteristics of CSR were analyzed by using an isolated carotid sinus preparation in Wistar rats. Animals were divided into two groups at random: unstressed group (n=42) and stressed group (n=41). According to the site of microinjection of histaminergic receptor antagonists, each group was subdivided into a group of intracerebroventricular injection (i.c.v.) and a group of microinjection into the nucleus of the solitary tract (NTS). The volume of injection into the lateral cerebroventricle and NTS was 5 microl and 1 micro1, respectively. Stressed groups were subjected to unavoidable electric foot-shock twice daily for a week, each session of foot-shock lasted 2 hours. The left and right carotid sinus regions were isolated from the systemic circulation under anesthesia with pentobarbital sodium in all rats. The intracarotid sinus pressure (ISP) was altered in a stepwise manner to trigger CSR from 0 to 280 mmHg at every step of 40 mmHg and 4 s, and then returned to 0 mmHg in similar steps. ISP and mean arterial pressure (MAP) were recorded simultaneously. ISP-MAP relationship curve was constructed by fitting to the logistic function with five parameters. The CSR parameters and the ISP-MAP relationship curve were separately compared statistically. The main results obtained are as follows. (1) Stress significantly shifted the ISP-MAP relationship curve upwards and obviously moved the middle part of ISP-Gain relationship curve downwards, and decreased the value of the MAP range and maximum gain (G(max)), but increased the threshold pressure (TP), saturation pressure (SP), set point and ISP at G(max) (ISP(Gmax)). (2) I.c.v. of H1 receptor antagonist chlorpheniramine (CHL, 5 microg) or H2 receptor antagonist cimetidine (CIM, 15 g) significantly diminished the above-mentioned changes in CSR performance induced by stress; the alleviative effect of CIM was less remarkable than that of CHL. The responses of CSR in stressed rats to H(1) or H(2) receptor antagonists generally occurred 20 min after the administration and lasted approximately for 15 min. (3) After microinjection of CHL (0.5 microg) or CIM (1.5 microg) into the NTS, the responses of CSR in stressed groups were similar to those after i.c.v. injection of CHL or CIM. (4) However, microinjection of CHL or CIM into the lateral cerebroventricle or the NTS could not completely abolish the stress-induced changes in CSR. These findings suggest that stress results in a resetting of CSR, a decrease in reflex sensitivity. The stress-induced changes in CSR may be mediated, at least in part, by activating the brain histaminergic system. The central histaminergic receptors (H(1) and H(2) receptors) may play an important role in the resetting of CSR under stress. The descending histaminergic pathway from the hypothalamus to NTS may be involved in these effects.

Effect of intracerebroventricular injection of histamine on carotid sinus baroreceptor reflex in anesthetized rats and its mechanism / 生理学报

The changes in carotid sinus baroreceptor reflex (CSR) performance induced by intracerebroventricular injection (i.c.v.) of histamine (HA) were investigated. The effects of pretreatment with HA receptors antagonists into the cerebroventricle or nucleus of solitary tract (NTS) on the responses of CSR to HA were also examined. Intracarotid sinus pressure (ISP)-mean arterial pressure (MAP) relationship curve was constructed by fitting to the logistic function with five parameters in 50 Wistar rats anesthetized with pentobarbital sodium. The left and right carotid sinus regions were isolated from the systemic circulation and the ISP was altered in a stepwise manner. The main results obtained are as follows. (1) i.c.v. injection of HA (100 ng) significantly shifted the ISP-MAP relationship curve upwards and moved the middle part of ISP-Gain relationship curve downwards, and reduced the MAP range and maximum gain (G(max)), but increased the threshold pressure (TP), saturation pressure (SP) and ISP at G(max) (ISP (Gmax)). (2) The pretreatment with H(1) or H(2) receptors antagonist, chlorpheniramine (CHL, 5 microg) or cimetidine (CIM, 15 microg), could obviously diminish the above-mentioned changes in CSR performance induced by HA, but the effect of CIM was less remarkable than that of CHL. (3) The pretreatment with both CHL and CIM (5 microg and 15 microg) at the same time abolished the responses of CSR performance to HA completely. (4) After microinjection of CHL (0.5 microg) or CIM (1.5 microg) into the NTS, the responses of CSR to HA were similar to those after i.c.v. CHL or CIM, but the change in TP was significantly decreased. These findings suggest that the intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity. The response of CSR to HA might be mediated by both central H(1) and H(2) receptors, especially by H(1) receptors. The effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to NTS. It is suggested that the HA receptors in the NTS play an important role in the responses of CSR to HA.