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.

Systemic Hypoxia Elevates Skeletal Muscle Interstitial Adenosine Levels in Humans

“…These findings suggest that in human skeletal muscle, adenosine plays a very important role in the regulation of local blood flow. Similar findings have been reported for rodent muscle 11 and canine muscle 9 ; it should be noted, however, that the level of hypoxia used in the present study is mild compared with those used in various animal models. It has been suggested, in animal preparations, that other compounds interact with adenosine to mediate the vasodilation associated with hypoxia.…”

“…However, it has been shown that during systemic hypoxia, the release of adenosine from canine skeletal muscle was increased. 9 Furthermore, it has been demonstrated in rodent muscle that adenosine largely mediates the vasodilation associated with systemic hypoxia 10,11 and that this vasodilation was dependent on nitric oxide synthesis. 10 However, whether these same substances or mechanisms are responsible for the hypoxia-induced vasodilatation in human skeletal muscle is unclear.…”

“…For example, it has been demonstrated that adenosine stimulates ATP-sensitive K ϩ channels on skeletal muscle to open, and the resulting release of K ϩ acts as a vasodilator. 11 More recently, it has been shown that vasodilation in rats induced by adenosine during systemic hypoxia was dependent on nitric oxide synthesis. 17 However, it is unclear whether a similar interaction between adenosine and nitric oxide exists in human skeletal muscle.…”

Chemoreceptors and cardiovascular control in acute and chronic systemic hypoxia

“…As a further part of the background, it was known that K + can induce vasodilatation by stimulating Na-K + ATPase activity in vascular smooth muscle and by opening inwardly rectifying K + channels (99). Thus, we hypothesised that adenosine released in skeletal muscle during systemic hypoxia opens K ATP channels on the skeletal muscle fibres leading to the release of K + which then contributes to the muscle vasodilatation (100).…”

Ion Channels

“…The effect of adenosine and GTP on KATP channels of rat isolated skeletal muscle fibres Adenosine activates KATP channels in both cardiac and arterial smooth muscle (Kirsch et al 1990; Dart & Standen, 1993), and it has recently been proposed that adenosine may release K+ from skeletal muscle fibres by activation of these channels (Marshall et al 1993 159 mm Cl-and 10 mm Hepes (pH 7 4) with or without adenosine (100 uM).…”