Sustained negative inotropism mediated by α‐adrenoceptors in adult mouse myocardial developmental conversion from positive response in the neonate

Article date: February 1995

By: Hikaru Tanaka, Shigeru Manita, Tomoyuki Matsuda, Mika Adachi, Koki Shigenobu, in Volume 114, Issue 3, pages 673-677

Inotropic responses to α‐adrenoceptor stimulation and the effects of antagonists were examined in isolated ventricular preparations from neonatal and adult mice.

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.

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.

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.

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 α1‐adrenoceptors, and modulate the overall inotropic response to NA in the adult.

Inotropic responses to α‐adrenoceptor stimulation and the effects of antagonists were examined in isolated ventricular preparations from neonatal and adult mice.

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.

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.

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.

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 α1‐adrenoceptors, and modulate the overall inotropic response to NA in the adult.

DOI: 10.1111/j.1476-5381.1995.tb17191.x

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