Baroreflex-mediated bradycardia but not tachycardia is blunted peripherally by intravenous mu-opioid agonists

We sought to test the hypothesis that an intravenous dose of H-Tyr-D-Arg-Phe-Lys-NH2, a highly mu-receptor selective opioid peptide, suppresses baroreflex sensitivity through a peripheral mechanism.

A transient change in mean arterial pressure was produced in chronically instrumented pregnant ewes by norepinephrine or sodium nitroprusside in the absence or in the presence of H-Tyr-D-Arg-Phe-Lys-NH2, a highly mu-selective opioid peptide. In some studies naloxone methiodide, a peripheral opioid antagonist, was infused starting 60 minutes before the administration of H-Tyr-D-Arg-Phe-Lys-NH2 and maintained for a total of 90 minutes. Linear plots were obtained when the changes in mean arterial pressure during the pressure rise were plotted against the changes in heart rate and the sensitivity of the baroreflex was derived as the slope of the linear regression line.

We observed (1) lower baroreflex sensitivity after H-Tyr-D-Arg-Phe-Lys-NH2 administration with a hypertensive stimulus; (2) unchanged baroreflex sensitivity after H-Tyr-D-Arg-Phe-Lys-NH2 administration with a hypotensive stimulus; and (3) unchanged baroreflex sensitivity after H-Tyr-D-Arg-Phe-Lys-NH2 administration with a hypertensive stimulus in the presence of naloxone methiodide.

H-Tyr-D-Arg-Phe-Lys-NH2 suppresses the hypertensive but not the hypotensive arm of the baroreflex through peripheral opioid receptors. These results suggest that mu-opioid receptors are present in the vagus nerves and that the activation of these opioid receptors inhibits reflex bradycardia in pregnant sheep.