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

• Published in: British journal of pharmacology 2009-01, Vol.132 (6), p.1209-1216
• Main Authors: Kingsbury, M P, Robinson, H, Flores, N A, Sheridan, D J
• Format: Article
• Language: English
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0703929

Reactive hyperaemia is a transient vasodilatation following a brief ischaemic period. ATP‐dependent K + (K ATP ) channels may be important in mediating this response, however it is unclear whether mitochondrial K ATP channels contribute to this in the heart. We examined the involvement of K ATP 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 K ATP channel inhibitor and 5‐hydroxy‐decanoic acid (5‐HD, 10 −4   M , n =10) a selective mitochondrial K ATP 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