Gender differences in the cardiac A1 adenosine receptor anti‐adrenergic effect

Abstract

There have been few reports on gender differences in cardiac adenosine receptors (AR). The A1AR modulation of the male and female cardiac β‐adrenergic response was studied in isolated perfused hearts (constant perfusion pressure, paced at 420 bpm) from C57BL/6 mice, monitoring left ventricular systolic pressure (LVSP), +dP/dT and –dP/dT (n≥4). To study the effects of estrogen withdrawal, a subset of females was studied 5–7 weeks post‐ovariectomy (OvX). No differences were seen between male (M), female (F) and OvX female (OvXF) hearts in baseline hemodynamic parameters, or in the β‐adrenergic response following isoproterenol (ISO) administration. In M, 2 nM ISO increased LVSP 86±8%, +dP/dT 131± 9% and –dP/dT 147±11%. 2 nM ISO responses were similar in F and OvXF. As shown in Table 1, pretreatment with 200 nM A1AR agonist CCPA produced an enhanced blunting of the 2 nM ISO response in F as compared to M and OvXF. These observations could be explained by differences in cardiac AR gene expression, with intact females showing 25% higher A1AR and 40% lower A2aAR expression than M and OvXF. These results suggest that ovarian hormones modulate AR gene expression, contributing to gender differences in AR function. Percent change from pre‐ ISO baseline in CCPA‐Treated Hearts LVSP +dP/dT −dP/dT Male 32± 5* 52±8* 67±11* Female 6±1 12±2 16±3 OvX Female 43±7† 83±18† 71±15† p<0.05 Female vs Male p<0.05 Female vs. OvX Female