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

1. 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. 2. We examined the involvement of K(...

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Bibliographic Details
Published in:British journal of pharmacology 2001-03, Vol.132 (6), p.1209-1216
Main Authors: Kingsbury, M P, Robinson, H, Flores, N A, Sheridan, D J
Format: Article
Language:English
Subjects:
Adenosine - metabolism
Animals
Disease Models, Animal
Dose-Response Relationship, Drug
Guinea Pigs
Heart Diseases - metabolism
Hyperemia - metabolism
Male
Membrane Proteins - metabolism
Membrane Proteins - physiology
Nitric Oxide - metabolism
Potassium Channels
Prostaglandins - metabolism
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Summary:1. 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. 2. 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. 3. 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). 4. 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 micromol) and diazoxide (42 nmol -- 2 micromol). Glibenclamide was most effective in blocking the hyperaemic response (by 87%, P
ISSN:0007-1188