AJP - Heart and Circulatory Physiology, Vol 249, Issue 1 102-H107, Copyright © 1985 by American Physiological Society
Restoration of coronary dilator action of adenosine in experimental diabetes
S. E. Downing
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.
