Enhanced inotropic responsiveness to alpha 1-adrenoceptor stimulation in isolated working hearts from diabetic rats

We compared the inotropic responsiveness to the alpha 1-adrenoceptor agonist cirazoline and the calcium entry promoter Bay K 8644 in isolated working hearts from streptozotocin (STZ) diabetic rats and age-matched controls. The maximal rate of contraction and cardiac output (CO) were unaffected by diabetes. The maximal rate of relaxation was significantly decreased in diabetic hearts as compared with controls. Cirazoline (10(-9)-10(-6) M) induced an increase in both maximal rate of contraction and relaxation in diabetic and control hearts. Notably, the maximal rate of contraction was significantly greater in diabetic hearts. Changes in maximal rate of relaxation were similar in both preparations. A significant increase in CO was observed in diabetic hearts, but not in controls. With Bay K 8644 (10(-9)-10(-6) M) added, the increase in maximal rate of contraction and relaxation as well as CO were not significantly different in the two preparations although the changes in maximal rate of relaxation tended to be decreased in diabetic hearts. Our results indicate that cardiac alpha 1-adrenoceptors appear to gain greater functional importance in regulation of myocardial inotropism in diabetes mellitus.