INCREASED ALPHA(1)-ADRENERGIC RESPONSIVENESS OF ALLOXAN-DIABETIC RAT ATRIA - EFFECTS OF INSULIN THERAPY AND THYROIDECTOMY

1. Experimental models of diabetes are increasingly used for the inves tigation of cardiovascular complications as well as other complication s due to diabetes mellitus. However, animal models have been used in r elatively few studies on the myocardial alpha(1)-adrenergic responses. Hence, this report describes the effect of alloxan-induced diabetes a nd insulin-treatment on the alpha(1)-adrenergic responses of this isol ated rat atria. 2. Alloxan-induced diabetes caused an increase in the alpha(1)-adrenergic responses assessed in isolated spontaneously beati ng rat atria. Both pD(2) and alpha(E) values for phenylephrine, an alp ha(1)-adrenergic agonist were increased in atria from rats with alloxa n diabetes. 3. Insulin treatment (4 IU/kg/day, s.c.) for 10 days norma lized the changes in diabetic rat atria. pD(2) and alpha(E) value for phenylephrine were slighly lower than those from control rats. Serum l evels of thyroid hormones returned to normal following insulin treatme nt as well. 4. The effect of insulin on the increased alpha(1)-adrener gic responses of rat atria due to alloxan diabetes seems to be related to thyroid hormone metabolism, since thyroidectomy also changed the a trial parameters measured. 5. The finding obtained in this study sugge st that experimentally-induced diabetes increases alpha(1)-adrenergic sensitivity of the rat atria possibly due to an increased receptor aff inity, but these changes can be reversed with insulin treatment.