Regional hemodynamic effects of nociceptin/orphanin FQ in the anesthetized rat

This study examined the vasodilator action of nociceptin, an endogenous opioid receptor-like ligand (ORL1), in thiobutabarbital-anesthetized rats, via the triple-isotope microspheres technique. Nociceptin (10, 30 nmol/kg, left ventricular injection) reduced mean arterial pressure (-27, -29 mm Hg), total peripheral resistance (-36, -41% of baseline) and heart rate (-8, -11% of baseline), but did not significantly affect cardiac output. The vehicle (0.9% NaCl) did not alter hemodynamics. Both doses of nociceptin caused similar changes in arterial flow and conductance of all tissues. Nociceptin increased flows to the skeletal muscle, slightly reduced flows to the caecum and colon, but did not alter flows to other organs and tissues. With flow normalized by pressure to reflect intrinsic vascular tone, nociceptin was found to increase arterial conductance of all tissues, except for the intestine, spleen, caecum and colon. Its dilator influence was greater in the skeletal muscle (≈250% of baseline conductance) than the lungs, heart, liver, stomach, kidneys, skin, testes and brain (140-160% of baseline). Thus, nociceptin causes generalized vasodilatation; its greatest influence is on the skeletal muscle bed.