The Brain Histaminergic System in Regulating the Cardiovascular System: Implications for Brain Mechanisms Underlying Exercise-Induced Cardiovascular Responses

A single bout of exercise induces a moderate increase in arterial pressure with marked tachycardia as a result of sympathoexcitation. However, the brain mechanisms underlying cardiovascular regulation during exercise still remain unknown. In this proceeding, we introduce our hypothesis that the brain histaminergic system plays an important role in regulating the cardiovascular system during exercise. The nucleus of the solitary tract (NTS) is one of the ideal brain sites for generating cardiovascular controls during exercise because it is known as a pivotal region which integrates the baroreceptor sensory information with other inputs such as muscle afferents and descending signals from the hypothalamic area. We found that activation of histamine receptor H1 expressed in the NTS neurons induced pressor and tachycardiac responses, and that the pressor response exhibited functional plasticity after long-term daily exercise. These findings suggest that H1 receptors in the NTS are involved in cardiovascular regulation during exercise. Since the NTS receives axons of histaminergic neurons located in the tuberomammillary nucleus (TMN) in the hypothalamus, the functional roles of TMN-NTS pathway have also been investigated. We electrically stimulated the TMN and found pressor and tachycardiac responses. Notably the pressor responses were partially inhibited by cetirizine, a H1 receptor antagonist, microinjected into the NTS whereas we failed to see the inhibitory effects on the heart rate response. Based on all these findings, we postulate that the TMN-NTS pathway has an important role in a central feed forward mechanism underlying pressor responses to exercise.