A link between adenosine, ATP-sensitive K+ channels, potassium and muscle vasodilatation in the rat in systemic hypoxia.

Abstract

1. In anaesthetized rats, systemic hypoxia evoked hyperventilation, tachycardia, a fall in arterial pressure, vasodilatation in skeletal muscle and increases in K+ concentration measured in arterial plasma ([K+]a), venous efflux from muscle ([K+]v) and in right atrial plasma ([K+]at). The ATP-sensitive potassium (K+ATP) channel inhibitor glibenclamide (10 or 20 mg kg-1 i.v.) reduced the muscle vasodilatation and increase in [K+]v, but had no significant effect on the other changes. 2. The adenosine receptor antagonist, 8-phenyltheophylline (8-PT, 10 mg kg-1 i.v.) had similar effects to glibenclamide. 3. Glibenclamide reduced the muscle vasodilatation evoked by the adenosine analogue, 2-chloroadenosine given i.v. (30 micrograms kg-1). 4. Infusion of adenosine (0.3 mg kg-1 min-1 for 5 min) into the hindlimb evoked muscle vasodilatation and an increase in [K+]v, both of which were abolished by 8-PT. 5. We propose that during systemic hypoxia, part of the muscle vasodilatation that can be attributed to adenosine is due to the action of K+, which is released from skeletal muscle fibres through glibenclamide-sensitive K+ channels (possibly K+ATP channels) that are activated by adenosine. This may be a general mechanism for the vasodilator influence of adenosine.