INCREASED RESPONSES TO ADENOSINE IN ISOLATED LEFT ATRIA FROM STREPTOZOTOCIN-DIABETIC RATS - EVIDENCE FOR THE INVOLVEMENT OF HYPOTHYROIDISM

Direct and indirect (antiadrenergic) inotropic effects of adenosine in the isolated left atrial preparations from streptozotocin-induced dia betic rats were examined by comparing with those from propylthiouracil -induced hypothyroid rats. Experimental diabetes was induced by a sing le i.v. injection of streptozotocin (45 mg/kg). Subsets of diabetic ra ts were treated daily with either insulin (6-8 units/kg) or triiodothy ronine (T-3; 8-10 mu g/kg). After 10 weeks, negative inotropic and ant iadrenergic effects of adenosine were assessed in the atria from nondi abetic, diabetic, insulin- or T-3-treated diabetic and hypothyroid rat s. Diabetic rats exhibited a significant increase in negative inotropi c and antiadrenergic effects of adenosine, as well as signs of hypothy roidism such as decreased thyroid hormone levels. The same changes in the adenosine effects also were noticed in the hypothyroid rats. In ou r study, the influence of T-3 treatment on the hyperreactivity of diab etic rat atria to adenosine also was examined by comparing with that o f insulin treatment. Both insulin and T-3 treatments restored the hype rreactivity to adenosine, with the exception of adenosine receptor aff inity (pD(2) value) calculated for the negative inotropic effect of ad enosine. These findings suggest that thyroid hormone deficiency is lik ely to be involved in the inotropic and antiadrenergic effects of aden osine on the left atria from rats with experimental diabetes for 10 we eks.