Cardiovascular and renal responses produced by central orphanin FQ/nociceptin occur independent of renal nerves

Abstract

The present study investigated the role of the renal nerves in mediating the cardiovascular and renal responses produced by the central administration of the opioid-like peptide orphanin FQ/nociceptin (OFQ/N) in conscious Sprague-Dawley rats. In conscious rats, OFQ/N (10 μg icv) produced a transient bradycardia and hypotension (nadir 20 min). Although renal sympathetic nerve activity (RSNA) initially remained unchanged, a delayed renal sympathoinhibitory response occurred after recovery (30 min) of blood pressure. By 30 and 70 min postinjection, RSNA decreased to 75 and 66% of control, respectively. Coinciding with the decrease in RSNA, central OFQ/N elicited a diuresis and antinatriuresis that occurred independent of changes in renal hemodynamics. In other studies, intracerebroventricular OFQ/N produced similar cardiovascular and renal excretory responses in bilaterally renal-denervated rats. Finally, in conscious sinoaortic deafferentiated rats, intracerebroventricular OFQ/N produced a rapid decrease in RSNA (55% of control, 10 min; 38% of control, 20 min) that paralleled the onset of the hypotension and bradycardia. These studies demonstrate that in conscious rats, intracerebroventricular OFQ/N produces a centrally mediated inhibition of RSNA which, due to activation of baroreflex mechanisms, is temporally dissociated from the hypotensive and bradycardia responses. As revealed in renal-denervated rats, the cardiovascular and renal excretory responses produced by central OFQ/N occur by a pathway that is independent of intact renal nerves or changes in renal hemodynamics.