Roles of the histaminergic receptors in the locus ceruleus in stress-induced carotid baroreflex resetting in rats / 中国应用生理学杂志

ABSTRACT

<p><b>AIM</b>To explore the roles of H1 and H2 receptors in the locus ceruleus (LC) in the carotid baroreflex (CBR) resetting resulted from foot-shock stress.</p><p><b>METHODS</b>Male SD rats were divided into two groups (n=18) at random unstressed and stressed group. The latter were subjected to unavoidable electric foot-shock twice daily for a week and each session of foot-shock lasted 2 hours. The left and right carotid sinus regions were isolated from the systemic circulation in all animals anesthetized with pentobarbital sodium. The intracarotid sinus pressure (ISP) was altered in a stepwise manner in vivo. ISP-mean arterial pressure (MAP), ISP-Gain relationship curves and reflex characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CBR performance induced by stress and the effects of microinjection with histaminergic receptors antagonists into the LC on the responses of CBR to stress were examined.</p><p><b>RESULTS</b>Stress significantly shifted the ISP-MAP relationship curve upwards (P < 0.05) and obviously moved the middle part of ISP-Gain relationship curve downwards (P < 0.05), and decreased the value of the MAP range and maximum gain (P < 0.05), but increased the threshold pressure, saturation pressure, set point and ISP at maximum gain (P < 0.05). Microinjection of selective H1 or H2 receptor antagonist, chlorpheniramine (CHL, 0.5 microg/microl) or cimetidine (CIM, 1.5 microg/microl) into the LC, significantly attenuated the above-mentioned changes in CBR performance induced by stress and the alleviate effect of CIM was less remarkable than that of CHL (P < 0.05). The responses of CBR under stress to H1 or H2 receptor antagonist generally occurred 20 min after the administration and lasted approximately for 16 min. Microinjection with the same dose of CHL or CIM into the LC in the unstressed group did not change CBR performance significantly (P > 0.05). However, microinjection of CHL or CIM into the LC could not completely abolish the stress-induced changes in CBR.</p><p><b>CONCLUSION</b>The stress results in a resetting of CBR and a decrease in reflex sensitivity. The stress-induced changes in CBR may be mediated, at least in part, by activating the brain histaminergic system. The H1 and H2 receptors in the LC, especially, Hi receptors may play an important role in the resetting of CBR under stress. The descending histaminergic pathway from the hypothalamus to LC may be involved in these effects. Moreover, the effects of stress on CBR also have other mechanisms.</p>