Restoration of coronary dilator action of adenosine in experimental diabetes

We have recently shown that the coronary dilator action of adenosine is reduced in animals with experimental diabetes mellitus. Effects of insulin replacement are reported in the present study. Lambs, age 6-17 days, were studied 1-2 days after induction of diabetes with alloxan (150 mg/kg; n = 6). These were compared with nondiabetic controls, age 4-15 days (n = 5). A third group was studied after 8-15 days of diabetes (n = 3). In the acute diabetics blood glucose was 362 +/- 48 mg/dl. Heart rate, dP/dtmax, and myocardial O2 consumption did not differ from controls, but pH tended to be lower (7.29 +/- 0.03). Adenosine was given by left ventricular infusion. Coronary flow changes were significantly lower at all infusion rates (3-15 micrograms X min-1 X kg-1) in the untreated diabetics. Dose-response curves before and after insulin (10 U/kg) were identical in controls. However, in the diabetics, insulin enhanced the dilator response to adenosine, and changes in coronary flow at each infusion rate did not differ from controls. Aminophylline (6 mg/kg) abolished or sharply reduced the dilator responses to adenosine in both controls and diabetics (P less than 0.01). Animals diabetic 1-2 wk were unresponsive to adenosine. But after insulin, the nucleoside elicited vigorous coronary dilatation. It is concluded that insulinopenic diabetes is accompanied by sharply reduced adenosine sensitivity of coronary resistance vessels. Sensitivity is restored by giving insulin. This hormone may modulate adenosine receptor properties of vascular smooth muscle.