Enhanced adrenergic sensitivity of the diabetic neonatal heart

We have previously shown that insulin reduces inotropic responses to norepinephrine (NE) in isolated cardiac muscle and intact hearts. This inhibition also occurs in vascular smooth muscle. The present study was designed to examine inotropic sensitivity of insulin-deficient diabetic (D) hearts to mixed (NE) and pure beta 1 (isoproterenol, Iso) adrenergic agonists. Lambs were given alloxan (150 mg/kg) and studied 2 days later (glucose, 392 mg/dl). Results from eight controls (C) were compared. All animals were prepared for measurements of ventricular performance and coronary flow (CF) under conditions of constant arterial pressure, aortic flow, and heart rate (paced). Dose-response dP/dtmax curves were obtained by stepped increases of agonist infusion (iv). Iso (40 ng X min-1 X kg-1) caused a 30% increase of CF in both C and D, but no change occurred with NE (0.4 micrograms X min-1 X kg-1). Myocardial O2 consumption did not differ among groups and was unaltered by either agonist. Initial values for heart rate and dP/dt did not differ between C and D. NE dose-response curves were consistently higher in D and the slopes significantly steeper than C. However, Iso curves did not differ. Insulin (10 U/kg) was given to both groups, and the studies were repeated. Dose-response curves in C did not differ significantly with either NE or Iso after insulin. In contrast, curves with both agonists were lower following insulin replacement in the diabetic animals. It is concluded that coronary resistance is reduced by beta-activation but unchanged by NE, which is also an alpha-agonist.(ABSTRACT TRUNCATED AT 250 WORDS)