Effect of nociceptin/orphanin FQ on venous tone in conscious rats

Nociceptin (orphanin FQ) is an endogenous agonist for the opioid receptor-like1 (ORL1) receptor. We investigated the effects of nociceptin on mean circulatory filling pressure, an index of venous tone. The effects of nociceptin (10, 30 nmol/kg, i.v.) and the vehicle (0.9% NaCl) on mean arterial pressure, heart rate and mean circulatory filling pressure were examined in two groups each of conscious rats: rats with, or without, ganglionic blockade through pretreatment with mecamylamine (1 mg/kg, i.v.) and noradrenaline (2 microg/kg min, i.v.). In the unblocked rats, both doses of nociceptin decreased mean arterial pressure and heart rate, and the high dose also decreased mean circulatory filling pressure. In the ganglionic-blocked rats, nociceptin did not alter heart rate but caused greater reductions of mean arterial pressure and mean circulatory filling pressure. The vehicle had no effects in any group. Therefore, nociceptin is a depressor agent with prominent direct venodilator and bradycardic action.