BAROREFLEX-MEDIATED BRADYCARDIA BUT NOT TACHYCARDIA IS BLUNTED PERIPHERALLY BY INTRAVENOUS MU-OPIOID AGONISTS

OBJECTIVE: We sought to test the hypothesis that an intravenous dose o f H-Tyr-D-Arg-Phe-Lys-NH2, a highly p-receptor selective opioid peptid e, suppresses baroreflex sensitivity through a peripheral mechanism. S TUDY DESIGN: 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-Ly s-NH2, a highly p-selective opioid peptide. In some studies naloxone m ethiodide, a peripheral opioid antagonist, was infused starting 60 min utes before the administration of H-Tyr-D-Arg-Phe-Lys-NH2 and maintain ed for a total of 90 minutes. Linear plots were obtained when the chan ges in mean arterial pressure during the pressure rise were plotted ag ainst the changes in heart rate and the sensitivity of the baroreflex was derived as the slope of the linear regression line. RESULTS: We ob served (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 hypote nsive stimulus; and (3) unchanged baroreflex sensitivity after H-Tyr-D -Arg-Phe-Lys-NH2 administration with a hypertensive stimulus in the pr esence of naloxone methiodide. CONCLUSION: H-Tyr-D-Arg-Phe-Lys-NH2 sup presses the hypertensive but not the hypotensive arm of the baroreflex through peripheral opioid receptors. These results suggest that p-opi oid receptors are present in the vagus nerves and that the activation of these opioid receptors inhibits reflex bradycardia in pregnant shee p.