Temperature-sensitive adenosine-mediated vasoconstriction in the skin microcirculation.

Abstract

The A1 and A2 adenosine receptor agonists (5'-(N-ethylcarboxamido)-adenosine, 2-chloroadenosine, adenosine (ADO) and N6-cyclohexyladenosine) were topically applied to 30- to 60-microns arterioles in the s.c. microcirculation of hamsters at different skin temperatures. Vasoconstrictor responses evoked by nanomolar concentrations of ADO and N6-cyclohexyladenosine were enhanced when local skin temperature (Ts) was increased, but unchanged when Ts was decreased. All these responses were antagonized by 8-phenyltheophylline, which suggests that temperature-sensitive vasoconstrictions were mediated by A1 receptors. In contrast, norepinephrine (10(-7) M) caused vasoconstrictions that were not enhanced at high Ts and were markedly reduced at low Ts, while angiotensin II (10(-8) M) caused vasoconstrictions that were temperature-insensitive. Vasodilator responses evoked by micromolar concentrations of ADO, 2-chloroadenosine and 5'-(N-ethylcarboxamido)-adenosine were temperature-insensitive. All these responses were antagonized by 8-phenyltheophylline, except those mediated by 10(-6) to 10(-4) M ADO, which can be explained by simple override of the receptor blockade. Thus, A1, but not A2, receptors show temperature-dependent actions in vivo, which suggests that temperature sensitivity could be an additional criterion for classification of ADO receptors.