Nociceptin modulates renal sympathetic nerve activity through a central action in conscious rats

Nociceptin, an endogenous agonist of the opioid receptor-like(1) receptor, is expressed in the hypothalamus, where it is implicated in autonomic nervous system control. However, the central actions of nociceptin on sympathetic nerve activity have not been studied. We investigated the effect of intracerebroventricularly administered nociceptin (2-10 nmol) on blood pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) in conscious rats and sinoaortic-denervated (SAD) rats. Intracerebroventricularly administered nociceptin resulted in a dose-dependent decrease in mean arterial pressure (MAP) and HR in intact rats. RSNA decreased 31.5 +/- 2.1 and 19.9 +/- 5.0% at a dose of 2 and 5 nmol, respectively. In SAD rats, MAP, HR, and RSNA decreased in a dose-dependent manner, and the maximum responses were larger than those in intact rats. The decrease in HR induced by nociceptin was blocked by propranolol but not by atropine, which indicates that nociceptin is acting by inhibiting cardiac sympathetic outflow. These nociceptin-induced depressor and bradycardic responses were not antagonized by pretreatment with naloxone and nocistatin. These findings suggest that central nociceptin may have a functional role in regulating cardiovascular and sympathetic nervous systems.