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Sustained negative inotropism mediated by α‐adrenoceptors in adult mouse myocardial developmental conversion from positive response in the neonate
Author(s) -
Tanaka Hikaru,
Manita Shigeru,
Matsuda Tomoyuki,
Adachi Mika,
Shigenobu Koki
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb17191.x
Subject(s) - phenylephrine , prazosin , inotrope , propranolol , yohimbine , medicine , endocrinology , atropine , stimulation , antagonist , blood pressure , receptor
1 Inotropic responses to α‐adrenoceptor stimulation and the effects of antagonists were examined in isolated ventricular preparations from neonatal and adult mice. 2 Phenylephrine, in the presence of propranolol, produced positive inotropic responses in neonates up to 1 week after birth, while it produced negative inotropic responses in mice older than 3 weeks. 3 Both positive and negative responses to phenylephrine in neonates and adults, respectively, were antagonized by prazosin, WB4101 (2‐([2,6‐dimethoxyphenoxyethyl]aminomethyl)‐1,4‐benzodioxane) and 5‐methylurapidil, but not by atropine, yohimbine or chlorethylclonidine. 4 Noradrenaline (NA) produced positive inotropic responses both in the neonate and adult; the responses were observed in a lower concentration‐range in the neonate than in the adult. WB4101 produced a significant leftward shift of the concentration‐response curve for noradrenaline in adult preparations while only a slight rightward shift was observed in the neonate. 5 Our results demonstrate the presence of α‐adrenoceptor‐mediated inotropic responses in the mouse ventricular myocardia. The response to phenylephrine changes from a positive to a negative effect during postnatal development. The responses are mediated by α 1 ‐adrenoceptors, and modulate the overall inotropic response to NA in the adult.