Hypothalamic opioid mu-receptors regulate discrete hemodynamic functions in the conscious rat

The effect of the selective mu-opioid agonist D-Ala2-Me-Phe4-Gly-ol5-enkephalin (DAGO), injected into the medial preoptic nucleus of hypothalamus, on cardiac output and regional blood flow was studied in the conscious rat and the effect of DAGO on renal sympathetic nerve activity and renal blood flow was studied in anesthetized rats. In conscious rats, injections of DAGO (1 or 10 nmol) into the preoptic nucleus increased the blood pressure in a dose-related manner. The maximum rises of mean arterial pressure and pulse pressure after the larger dose were +23 +/- 5 mmHg (mean +/- SEM, P less than 0.01) and +17 +/- 3 mmHg (P less than 0.01), respectively. A small dose (0.1 nmol) increased heart rate (+47 +/- 13 bpm, P less than 0.05); the 1 nmol dose produced bradycardia (-39 +/- 11 bpm, P less than 0.05), while the 10 nmol dose initially decreased heart rate (-68 +/- 15 bpm (P less than 0.01) and then gradually increased heart rate to a maximum of +74 +/- 13 bpm, (P less than 0.01). A long-lasting increase in cardiac output was also elicited by DAGO, with maximum changes after 1 and 10 nmol of +14 +/- 6% and +22 +/- 7% (P less than 0.01), respectively. Blood flow in the hindquarters increased after DAGO but the mesenteric and renal blood flow decreased in a dose-related manner. Significant responses in hindquarter and mesenteric blood flow after DAGO were independent of systemic hemodynamic responses at the dose of 0.1 nmol. The vascular resistance in the hindquarters significantly decreased after a small dose of DAGO while the larger doses dose-dependently increased mesenteric and renal vascular resistance. A crucial role of the sympathetic nervous system in the hemodynamic effects of DAGO was demonstrated: (1) by the profound activation of renal sympathetic nerve activity after injections of DAGO (1 nmol/100 nl) into the preoptic nucleus, (2) by blockade of the pressor, tachycardic and regional hemodynamic effects of DAGO (1 nmol) by the ganglion blocker chlorisondamine (5 mg/kg i.v.). The results suggest that the pressor effect of DAGO in preoptic nucleus is due primarily to an increase in cardiac output. The differential changes in blood flow in organs further suggest that the opioid mu-receptors in the preoptic nucleus might be involved in the integration of peripheral blood flow in the hypothalamus during affective behavior.