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 nervo us system control. However, the central actions of nociceptin on sympatheti c nerve activity have not been studied. We investigated the effect of intra cerebroventricularly 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 admini stered nociceptin resulted in a dose-dependent decrease in mean arterial pr essure (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 R SNA decreased in a dose-dependent manner, and the maximum responses were la rger than those in intact rats. The decrease in HR induced by nociceptin wa s blocked by propranolol but not by atropine, which indicates that nocicept in is acting by inhibiting cardiac sympathetic outflow. These nociceptin-in duced depressor and bradycardic responses were not antagonized by pretreatm ent with naloxone and nocistatin. These findings suggest that central nocic eptin may have a functional role in regulating cardiovascular and sympathet ic nervous systems.