Myocardial chronotropic and inotropic responsiveness in vitro after chronic alpha 1-adrenoreceptor blockade in the rat

1. Positive chronotropic and inotropic myocardial responses to different adrenoreceptor agonists were studied using isolated right atria and left ventricular papillary muscles from rats treated orally for 5 weeks with prazosin, an alpha 1-antagonist, or vehicle (distilled water). 2. Chronotropic responses to the beta-adrenoreceptor agonists isoprenaline and salbutamol were similar in atria from both groups of rats, with no differences in their basal rates, maximum rate increases or pD2 values for either agonist. 3. Basal contractile force of field-stimulated papillary muscles was similar in both prazosin-treated (0.089 +/- 0.014 g mg-1) and control groups (0.104 +/- 0.035 g mg-1). In response to noradrenaline, force increased maximally by 145 +/- 30% and 131 +/- 30% above resting levels respectively, and pD2 values for this beta- and alpha-agonist showed no changes after chronic prazosin treatment. Inotropic responses to isoprenaline were also not different with maximum increases in force of 94.5 +/- 20.2% for prazosin-treated and 84.5 +/- 18.5% for controls, and similar pD2 values. 4. However, in response to the alpha 1-agonist phenylephrine (in the presence of propranolol), maximum increases in force were greater in relation to the noradrenaline maxima after prazosin treatment (48.8 +/- 4.2%) than in controls (32.0 +/- 4.3%, P less than 0.02). pD2 values for phenylephrine were also significantly higher after long-term alpha 1-blockade (5.71 +/- 0.10 vs 5.30 +/- 0.19 for controls, P less than 0.05). 5. Long-term alpha 1-blockade in the rat therefore led to supersensitivity of alpha 1-mediated inotropism in the heart, but both beta-mediated inotropic and chronotropic responses were unaffected. These results show selectivity of action of chronic prazosin treatment on alpha 1-receptors in the rat heart.