Nociceptin/orphanin FQ increases blood pressure and heart rate via sympathetic activation in sheep

This study was undertaken to examine the cardiovascular effects of nocicept in/Orphanin FQ (OFQ). Nociceptin/OFQ (10-300 nmol/kg, IV) stimulates an inc rease in mean blood pressure (MBP) and heart rate (HR) in chronically cathe terized sheep. Pretreatment with phenoxybenzamine (5 mg/kg) attenuated the presser response, consistent with sympathetically mediated vasoconstriction . Furthermore, the lack of a reflex bradycardia suggests either blunting of the baroreflex by nociceptin/OFQ or direct beta-adrenergic activation. The bradycardic response to norepinephrine (0.6 mu g/kg, IV) remained intact a fter nociceptin/OFQ administration, demonstrating that nociceptin/OFQ does not blunt the baroreflex. Additionally, the increase in HR was completely r eversed by pretreatment with propranolol. These data suggest that nocicepti n/OFQ plays a role in cardiovascular regulation via sympathetic activation. (C) 1999 Elsevier Science Inc. All rights reserved.