Activation of cardiac P2X receptors in hypertensive rats displays exaggerated sympathoexcitatory reflexes

Abstract

The concurrence of hypertension and ischemia leads to increased morbidity and fatality in individuals compared to myocardial ischemia alone. Ischemic mediators activate cardiac sympathetic afferents and evoke cardiac sympathoexcitatory reflex (CSR) responses. Recent work has revealed that the ischemic mediator ATP stimulates ischemic‐sensitive cardiac sympathetic afferents mostly through activation of P2X receptors. However, little is known about these mediators in CSR responses of hypertensive animals. We therefore hypothesized that activation of P2X receptors in the cardiac sensory nerves exaggerates CSR responses in hypertensive compared to normotensive animals. Arterial pressure and renal sympathetic nerve activity in response to intrapericardial injection of the P2X receptor agonist α,β‐meATP (31 to 125 nmol) were recorded in four groups of rats (n=5/each group), two of which were hypertensive, including cold‐induced hypertension (CIH) and spontaneous hypertension (SHR). The other two groups included SD and WKY normotensive rats. A larger CSR was evoked in response to intrapericardial α,β‐meATP in hypertensive (CIH and SHR) rats vs. normotensive (SD and WKY) rats in a dose‐dependent manner. In all four groups, intrapericardial injection of vehicle produced no CSR response. These data suggest that cardiac sympathoexcitatory reflexes induced by activation of P2X receptors are exacerbated in hypertensive animals. (Funded by HL‐66217)