Testosterone-augmented contractile responses to α1- and β1-adrenoceptor stimulation are associated with increased activities of RyR, SERCA, and NCX in the heart

We hypothesized that testosterone at physiological levels enhances cardiac contractile responses to stimulation of both α1- and β1-adrenoceptors by increasing Ca2+ release from the sarcoplasmic reticulum (SR) and speedier removal of Ca2+ from cytosol via Ca2+-regulatory proteins. We first determined the left ventricular developed pressure, velocity of contraction and relaxation, and heart rate in perfused hearts isolated from control rats, orchiectomized rats, and orchiectomized rats without and with testosterone replacement (200 μg/100 g body wt) in the presence of norepinephrine (10−7 M), the α1-adrenoceptor agonist phenylephrine (10−6 M), or the nonselective β-adrenoceptor agonist isoprenaline (10−7 M) in the presence of 5 × 10−7 M ICI-118,551, a β2-adrenoceptor antagonist. Next, we determined the amplitudes of intracellular Ca2+ concentration transients induced by electrical stimulation or caffeine, which represent, respectively, Ca2+ release via the ryanodine receptor (RyR) or releasable Ca2+ in the ...