Enhanced adrenergic sensitivity of the diabetic neonatal heart
Downing, S.E.; Lee, J.C.
American Journal of Physiology 248(1 Pt 2): H125-H131
1985
ISSN/ISBN: 0002-9513 PMID: 3881980 Document Number: 247926
Insulin reduces inotropic responses to norepinephrine (NE) in isolated cardiac muscle and intact hearts. This inhibition also occurs in vascular smooth muscle. Inotropic sensitivity of insulin-deficient diabetic (D) hearts to mixed (NE) and pure .beta.1 (isoproterenol, Iso) adrenergic agonists was examined. Lambs were given alloxan (150 mg/kg) and studied 2 days later (glucose, 392 mg/dl). Results from 8 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 (i.v.). Iso (40 ng .cntdot. min-1 .cntdot. kg-1) caused a 30% increase of CF in both C and D, but no change occurred with NE (0.4 .mu.g .cntdot. min-1 .cntdot. 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. 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. Curves with both agonists were lower following insulin replacement in the diabetic animals. Evidently, coronary resistance is reduced by .beta.-activation but unchanged by NE, which is also an .alpha.-agonist. Enhanced positive inotropic responses to NE (but not Iso) in D is consistent with greater .alpha.-receptor sensitivity, as shown with methoxamine. In lambs, acute insulin treatment decreases agonist sensitivity of D but not nondiabetics.