Effects of prolonged isoproterenol infusion on cardiac and vascular responses to adrenoceptor agonists.

In vitro responses of cardiac and vascular smooth muscle to both adrenoceptor agonists and phosphodiesterase inhibitors were studied in tissues from either saline- or isoproterenol-infused rats. After chronic isoproterenol infusion the sigmoidal relationship between concentration of acutely administered isoproterenol and inotropic response of cardiac muscle was shifted to the right; the maximum response was decreased by approximately 40%. Inotropic responses were attenuated further by the beta adrenoceptor antagonist, propranolol. By contrast, quantitatively comparable inotropic responses to phenylephrine were not altered after isoproterenol infusion. However, they were blocked by the selective alpha adrenoceptor antagonist, prazosin, but were not affected by propranolol. Inotropic effects of the phosphodiesterase inhibitor, isobutylmethylxanthine, were comparable in tissues from either saline- or isoproterenol-infused rats. Similar results were obtained in vascular tissues. Portal veins and aortas from isoproterenol-infused rats were less responsive to the acute relaxant properties of the beta adrenoceptor agonists, isoproterenol and salbutamol. However, as in cardiac muscle, relaxant effects to phosphodiesterase inhibitors (isobutylmethylxanthine and papaverine) were not attenuated. In addition, contraction to norepinephrine was comparable in tissues from either saline- or isoproterenol-infused rats. These data indicate that isoproterenol infusion attenuates beta adrenoceptor-mediated responses of vascular and cardiac muscle to similar degrees but does not alter responses to either alpha adrenoceptor agonists or phosphodiesterase inhibitors.