A link between adenosine, ATP-sensitive K+ channels, potassium and muscle vasodilatation in the rat in systemic hypoxia.
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.
Marshall
J M
JM
Department of Physiology, Medical School, Birmingham.
Thomas
T
T
Turner
L
L
D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005905:Glyburide / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D009132:Muscles / Q000098:blood supply; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D015221:Potassium Channels; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D015762:2-Chloroadenosine; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; D011188:Potassium; D005905:Glyburide