COMPARATIVE EFFECTS ON BLOOD-PRESSURE AND HEART-RATE OF DYNORPHIN A(1-13) IN ANTERIOR HYPOTHALAMIC AREA, POSTERIOR HYPOTHALAMIC AREA, NUCLEUS-TRACTUS-SOLITARIUS, AND LATERAL CEREBRAL VENTRICLE IN THE RAT

The objective of this study was to explore the effects of the endogenous opioid peptide dynorphin A(1-13) on the CNS regulation of blood pressure and heart rate. Wistar rats, anesthetized with pentobarbital and halothane, received dynorphin A(1-13) microinjected into the anterior hypothalamus area (AHA), the posterior hypothalamic area (PHA), the nucleus tractus solitarius (NTS), or the lateral cerebral ventricle (ICV). Dynorphin A(1-13), 20 (12 nmol) or 30 mug ICV, produced significant (p < 0.05) reductions in blood pressure and heart rate. Naloxone, 50 mug/kg ICV, completely prevented the blood pressure response and significantly (p < 0.05) blunted the heart rate response to the highest dynorphin concentration, 30 mug ICV (18 nmol). Dynorphin A(1-13), 5 mug, in the NTS significantly (p < 0.05) decreased systolic and diastolic blood pressure and heart rate with the response being evident 10 min and persisting for 30 min after injection. In contrast, the same dose of dynorphin A(1-13) in the AHA produced an immediate, marked, and significant (p < 0.05) decrease in systolic and diastolic blood pressure and heart rate that attained its maximum 1-3 min and retumed rapidly towards baseline levels. Dynorphin A(1-13), 5 or 10 mug in the posterior hypothalamic area, was not associated with any change in blood pressure or heart rate. Injection of the diluent at any site was not associated with any changes in blood pressure or heart rate. The maximum change in blood pressure with dynorphin was greater in the AHA than NTS, and the maximum change in heart rate was greater in the NTS than AHA. These data indicate a potential role for dynorphin as a modulator of the CNS regulation of blood pressure and cardiac rate, and this is mediated in part through different areas in the brain that maybe localized to the anterior hypothalamic area and nucleus tractus solitarius but not the posterior hypothalamic area.