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

This study was undertaken to examine the cardiovascular effects of nociceptin/Orphanin FQ (OFQ). Nociceptin/OFQ (10-300 nmol/kg, IV) stimulates an increase in mean blood pressure (MBP) and heart rate (HR) in chronically catheterized sheep. Pretreatment with phenoxybenzamine (5 mg/kg) attenuated the pressor 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 microg/kg, IV) remained intact after nociceptin/OFQ administration, demonstrating that nociceptin/OFQ does not blunt the baroreflex. Additionally, the increase in HR was completely reversed by pretreatment with propranolol. These data suggest that nociceptin/OFQ plays a role in cardiovascular regulation via sympathetic activation.