The involvement of ATP‐sensitive potassium channels and adenosine in the regulation of coronary flow in the isolated perfused rat heart

1 The roles of adenosine 5′‐triphosphate (ATP)‐sensitive potassium channels (K ATP ) and endogenous adenosine in the regulation of coronary flow have been assessed in the isolated, buffer‐perfused heart of the rat. 2 In the presence of glibenclamide 10 μ m there was a significant ( P < 0.001) reduction in coronary flow from a baseline value of 8.78 ± 0.76 ml min −1 g _1 to 3.89 ± 0.59 ml min −1 g −1 . This change was accompanied by a significant ( P <0.01) reduction in cardiac mechanical performance as shown by the decrease in the pressure‐rate product from 21,487 ± 2,577 mmHg min −1 to 6,950 ± 1,104 mmHg min −1 . 3 The non‐selective adenosine antagonist 8‐phenyltheophylline (10 μ m ) also caused a significant ( P <0.001) reduction in coronary flow from a basal value of 10.4 ± 0.6 ml min −1 g _1 to 6.32 ± 0.60 ml min −1 g _1 . The subsequent addition of glibenclamide, in the presence of 8‐phenyltheo‐phylline, brought about a further significant ( p <0.001) reduction in coronary flow to 3.05 ± 0.55 ml min −1 g _1 and this value was similar to that in the presence of glibenclamide alone. 4 In hearts perfused under constant flow conditions, exogenous adenosine caused dose‐related reductions in coronary perfusion pressure described by a maximum reduction in pressure of 30.7 ± 3.9 mmHg and an ED 50 of 977 ± 813 pmol. Addition of glibenclamide caused a significant ( P <0.01) increase in coronary perfusion pressure of 44.7 ± 7.2 mmHg and a significant ( P <0.05) rightward shift of the dose‐response curve for the depressor effects of adenosine (ED 50 = 13.5 ± 3.8 nmol), with a depression ( P <0.05) of the maximum (16.3 ± 2.4 mmHg). 5 In conclusion, both K Atp and endogenous adenosine make major contributions towards coronary vascular tone and the regulation of coronary flow in the rat isolated heart. Furthermore, in the coronary vasculature a significant proportion of the vasodilator action of adenosine is mediated through the activation of K Atp