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Selective cardiovascular and neuroendocrine effects of a kappa‐opioid agonist in the nucleus tractus solitarii of rats.
Author(s) -
Carter D A,
Lightman S L
Publication year - 1985
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1985.sp015829
Subject(s) - endocrinology , medicine , agonist , vasopressin , (+) naloxone , chemistry , opioid , receptor
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.