Increased Alpha(1)-Adrenergic Responsiveness of Alloxan-Diabetic Rat Atria - Effects of Insulin Therapy and Thyroidectomy

Abstract

1. Experimental models of diabetes are increasingly used for the investigation of cardiovascular complications as well as other complications due to diabetes mellitus. However, animal models have been used in relatively few studies on the myocardial alpha(1)-adrenergic responses. Hence, this report describes the effect of alloxan-induced diabetes and insulin-treatment on the alpha(1)-adrenergic responses of this isolated rat atria. 2. Alloxan-induced diabetes caused an increase in the alpha(1)-adrenergic responses assessed in isolated spontaneously beating rat atria. Both pD(2) and alpha(E) values for phenylephrine, an alpha(1)-adrenergic agonist were increased in atria from rats with alloxan diabetes. 3. Insulin treatment (4 IU/kg/day, s.c.) for 10 days normalized the changes in diabetic rat atria. pD(2) and alpha(E) value for phenylephrine were slighly lower than those from control rats. Serum levels of thyroid hormones returned to normal following insulin treatment as well. 4. The effect of insulin on the increased alpha(1)-adrenergic responses of rat atria due to alloxan diabetes seems to be related to thyroid hormone metabolism, since thyroidectomy also changed the atrial parameters measured. 5. The finding obtained in this study suggest that experimentally-induced diabetes increases alpha(1)-adrenergic sensitivity of the rat atria possibly due to an increased receptor affinity, but these changes can be reversed with insulin treatment.