Title

Myocardial adenosine A1-receptor sensitivity during juvenile and adult stages of maturation

UMMS Affiliation

Department of Physiology

Date

3-5-1998

Document Type

Article

Subjects

Adenosine; Adenylate Cyclase; Adrenergic beta-Agonists; Aging; Animals; Heart; Heart Rate; Isoproterenol; Male; Myocardial Contraction; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P1; Vasodilator Agents; Xanthines

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

In the heart, endogenous adenosine attenuates the beta-adrenergic-elicited increase in contractile performance via activation of adenosine A1 receptors. It has been recently reported that this function of adenosine becomes more pronounced with myocardial maturation. The purpose of the present study was to determine whether mature hearts possess a greater sensitivity than immature hearts to this antiadrenergic effect of adenosine. Isolated perfused hearts or atria from immature (ca. 23 days) and mature (ca. 80 days) rats were stimulated with isoproterenol (Iso), a beta-adrenergic agonist, at 10(-8) M and concomitantly exposed to increasing concentrations of 2-chloro-N6-cyclopentyladenosine (CCPA), a highly selective and potent adenosine A1-receptor agonist, from 10(-12) to 10(-6) M. CCPA at 10(-10)-10(-6) M dose dependently reduced the Iso-elicited contractile response more in immature than in mature hearts or atria. At 10(-6) M, CCPA reduced the Iso-elicited contractile response by 103% in immature hearts and by 55% in mature hearts. These effects of CCPA were attenuated by the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine at 10(-7) M. In additional experiments, CCPA exhibited similar effectiveness in reducing the spontaneous heart rate of immature and mature hearts, an effect also mediated by activation of adenosine A1 receptors. Similar to CCPA, the adenosine A1-receptor agonist R-N6-(2-phenylisopropyl)adenosine reduced the Iso-elicited contractile response more in immature than in mature hearts, albeit with less effectiveness than CCPA. In agreement with these results, CCPA reduced Iso-elicited adenylyl cyclase activity more in immature than in mature hearts. Overall, in contrast with our original hypothesis, these results indicate that immature hearts display greater sensitivity than mature hearts to the antiadrenergic effect of adenosine A1-receptor activation.

Rights and Permissions

Citation: Am J Physiol. 1998 Feb;274(2 Pt 2):H627-35.

Related Resources

Link to article in PubMed

Journal Title

The American journal of physiology

PubMed ID

9486267