Investigation of mechanisms that mediate reactive hyperaemia in guinea‐pig hearts: role of KATP channels, adenosine, nitric oxide and prostaglandins

Reactive hyperaemia is a transient vasodilatation following a brief ischaemic period. ATP‐dependent K+ (KATP) channels may be important in mediating this response, however it is unclear whether mitochondrial KATP channels contribute to this in the heart. We examined the involvement of KATP channels and the relative role of mitochondrial channels as mediators of coronary reactive hyperaemia and compared them to mechanisms involving NO, prostaglandins and adenosine in the guinea‐pig isolated heart. Reactive hyperaemic vasodilatation (peak vasodilator response and flow debt repayment) were assessed after global zero‐flow ischaemia (5 – 120 s) in the presence of nitro‐L‐arginine methyl ester (L‐NAME, 10−5 M, n=9), 8‐phenyltheophylline (8‐PT, 10−6 M, n=12) and indomethacin (10−5 M, n=12). Glibenclamide (10−6 M, n=12) a non‐selective KATP channel inhibitor and 5‐hydroxy‐decanoic acid (5‐HD, 10−4 M, n=10) a selective mitochondrial KATP channel inhibitor were also used. The specificity of the effects of glibenclamide and 5‐HD (n=6 each) were confirmed using pinacidil (38 nmol – 10 μmol) and diazoxide (42 nmol – 2 μmol). Glibenclamide was most effective in blocking the hyperaemic response (by 87%, P