Coronary dilator actions of adenosine and CO2 in experimental diabetes

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Abstract
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.