Title

Antiadrenergic effects of adenosine in pressure overload hypertrophy

UMMS Affiliation

Department of Physiology; Department of Medicine, Division of Cardiovascular Medicine

Date

3-13-2001

Document Type

Article

Subjects

Adenosine; Adrenergic Antagonists; Adrenergic beta-Agonists; Animals; Blood Pressure; Body Weight; Caffeine; Calcium; Cardiomegaly; Cells, Cultured; Coronary Circulation; Disease Models, Animal; Echocardiography; Inosine; Isoproterenol; Male; Myocardial Contraction; Myocardium; Organ Size; Perfusion; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P1

Disciplines

Physiology

Abstract

In the present study, we sought to evaluate whether the antiadrenergic action of adenosine in the heart is altered in pressure overload hypertrophy produced in rats by suprarenal aortic banding. Epicardial and coronary effluent adenosine and inosine concentrations and release were significantly elevated in compensated pressure overload hypertrophy but not in hearts with left ventricular failure. In pressure overload hearts, the contractile response to beta-adrenergic stimulation was less inhibited by incremental concentrations of either adenosine or the selective A(1) receptor agonist chloro-N:(6)-cyclopentyl adenosine than in controls. Furthermore, the extent of desensitization to the antiadrenergic actions of adenosine in pressure overload hypertrophy appeared to be proportional to the extent of chamber dilation and dysfunction. A 60-minute infusion of adenosine produced a sustained antiadrenergic effect that lasted up to 45 minutes after the infusion was terminated in both controls and hearts with compensated hypertrophy. This effect was not observed in the decompensated left ventricular failure group. Subsequent infusion with adenosine of the A(2A) receptor antagonist 8-(3-chlorostyryl)-caffeine to counteract the proadrenergic effect of A(2A) receptor stimulation did not alter the decreased sensitivity to the antiadrenergic actions of adenosine in hypertrophied hearts. Finally, isolated myocytes from hypertrophied hearts demonstrated a decreased ability to suppress isoproterenol-elicited increases in [Ca(2+)](i) transients in the presence of adenosine and the A(2A) receptor antagonist compared with myocytes from control hearts. Myocardial adenosine concentrations increase during the compensated phase of pressure overload hypertrophy but then decrease when there is evidence of decompensation. The antiadrenergic actions of adenosine transduced via the myocardial A(1) receptor are diminished in pressure overload hypertrophied hearts. These factors may render these hearts more vulnerable to the detrimental effects of chronically increased sympathetic activity.

Rights and Permissions

Citation: Hypertension. 2001 Mar;37(3):862-8.

Related Resources

Link to article in PubMed

PubMed ID

11244009