Selective cardiovascular and neuroendocrine effects of a kappa-opioid agonist in the nucleus tractus solitarii of rats

Abstract

The cardiovascular and neuroendocrine effects of a selective kappa-opiate receptor agonist (U50488H) microinjected into the nucleus tractus solitarii have been investigated in urethane-anaesthetized rats. Comparative experiments were conducted using 8-arginine vasopressin (AVP)-deficient Brattleboro rats and an opiate agonist selective for delta receptors. Unilateral injection of U50488H elicited a significant dose-dependent increase in mean arterial pressure and a small decrease in heart rate in Sprague-Dawley rats. The pressor effect was blocked preferentially by the relatively selective kappa-receptor antagonist MR2266BS compared to naloxone. Bilateral injections of U50488H elicited a relatively greater increase in mean arterial pressure than unilateral injections and a significant decrease in heart rate. U50488H did not elicit a pressor effect in Brattleboro rats, whereas a marked response (associated with a significant increase in AVP secretion) was found in parent strain Long-Evans rats. In contrast, no such differential effects in the response of Brattleboro and Long-Evans rats were observed in parallel experiments using equimolar doses of the selective delta-opiate agonist Tyr-D-Ser-Gly-Phe-Leu-Thr which elicited a transient pressor response. An antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylene-propionic acid)2-(0-methyl) tyrosine] arginine vasopressin (1,d(CH2)5Tyr(ME)AVP) specific for the vasopressor action of AVP blocked the U50488H-induced pressor response in a dose-dependent manner when administered intravenously 10 min prior to the kappa agonist, but did not significantly attenuate the response to the delta agonist. Conversely, the U50488H-induced response was not modified by pre-treatment with phenoxybenzamine whereas the delta-agonist pressor response was completely blocked by it. The results provide evidence for specific kappa-opiate cardiovascular and neuroendocrine responses in the nucleus tractus solitarii and suggest that a kappa-receptor mechanism, possibly involving a peptide of the dynorphin group as the endogenous ligand, may operate in the central control of blood pressure and AVP secretion.