AJP - Heart and Circulatory Physiology, Vol 243, Issue 2 252-H258, Copyright © 1982 by American Physiological Society
Coronary dilator actions of adenosine and CO2 in experimental diabetes
S. E. Downing, J. C. Lee and E. M. Weinstein
We have previously shown that coronary regulation is altered in the
diabetic lamb. In the present investigation the effects of hypercapnic
acidosis (increases CO2) and adenosine on coronary sinus flow (CF; ml .
min-1 . 100 g-1 LV) were assessed in 13 controls and 7 diabetic lambs
(glucose 1,084 +/- 193 mg/dl) given alloxan (150 mg/kg) 2 days prior to
study. All measurements were made under conditions of constant aortic
pressures and cardiac output. Left ventricular (LV) performance was
continuously recorded; O2 content, O2 and CO2 partial pressure, pH, and
glucose concentrations were compared in simultaneous sinus and arterial
samples. Dose-response curves (0.30 micrograms . min-1 . kg-1) indicated a
linear relationship between adenosine and CF. At infusion rates of 30 (iv)
or 3 (LV) micrograms . min-1 . kg-1 adenosine increased CF by 30 and 21 ml
. min-1 . 100 g-1 LV, respectively in control (P less than 0.001) but not
in diabetic lambs. With increases CO2 (80 mmHg; pH 6.95), CF increased
substantially (control 60 ml; diabetic 45 ml) in both groups (P less than
0.001). The dilator action of adenosine was enhanced in control during
increases CO2, and significant responses to adenosine appeared in the
diabetic group. It is concluded that increases [H+] has a potent direct
coronary dilator action in both control and diabetic lambs and enhances
responsiveness to adenosine. Sensitivity to adenosine is reduced in
diabetics, and this subsensitivity is largely reversed by hypercapnic
acidosis.
