Increased responses to adenosine in isolated left atria from streptozotocin-diabetic rats: evidence for the involvement of hypothyroidism.

Abstract

Direct and indirect (antiadrenergic) inotropic effects of adenosine in the isolated left atrial preparations from streptozotocin-induced diabetic rats were examined by comparing with those from propylthiouracil-induced hypothyroid rats. Experimental diabetes was induced by a single i.v. injection of streptozotocin (45 mg/kg). Subsets of diabetic rats were treated daily with either insulin (6-8 units/kg) or triiodothyronine (T3; 8-10 micrograms/kg). After 10 weeks, negative inotropic and antiadrenergic effects of adenosine were assessed in the atria from nondiabetic, diabetic, insulin- or T3-treated diabetic and hypothyroid rats. Diabetic rats exhibited a significant increase in negative inotropic and antiadrenergic effects of adenosine, as well as signs of hypothyroidism such as decreased thyroid hormone levels. The same changes in the adenosine effects also were noticed in the hypothyroid rats. In our study, the influence of T3 treatment on the hyperreactivity of diabetic rat atria to adenosine also was examined by comparing with that of insulin treatment. Both insulin and T3 treatments restored the hyperreactivity to adenosine, with the exception of adenosine receptor affinity (pD2 value) calculated for the negative inotropic effect of adenosine. These findings suggest that thyroid hormone deficiency is likely to be involved in the inotropic and antiadrenergic effects of adenosine on the left atria from rats with experimental diabetes for 10 weeks.