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

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Abstract
1. 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. 2. 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. 3. 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 .epsilon.-opiate agonist Tyr-D-Ser-Gly-Phe-Leu-Thr which elicited a transient pressor response. 4. An antagonist [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylene-propionic acid)2-(O-methyl) tyrosine] arginine vasopressin (1,d(CH2) 5 Tyr (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. 5. 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.

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