INHIBITION OF ARTERIOLE ALPHA(2)-ADRENOCEPTOR BUT NOT ALPHA(1)-ADRENOCEPTOR CONSTRICTION BY ACIDOSIS AND HYPOXIA IN-VITRO

We have found that hypoxia and acidosis inhibit constriction by alpha(2D)-adrenoceptors but not by alpha(1D)-adrenoceptors on arterioles of rat skeletal muscle, facilitating local. metabolic control of blood flow. When activated by full agonists like norepinephrine, this alpha(2D)-constriction relies on Ca2+ influx through dihydropyridine-sensitive, voltage-operated Ca2+ channels (VOC), while alpha(1D)-constriction does not. The purpose of the present study was to examine the dose sensitivity of this selective metabolic inhibition of alpha(2D)-constriction and determine whether inhibition of VOCs is involved. Changes in lumen diameter of microcannulated arterioles isolated from rat skeletal muscle (107 +/- 3 mu m control diam) were measured by videomicroscopy for bath-added agents. Decreases in pH (7.4-7.0) or P-O2 (70 to 10 mmHg) caused graded inhibition of alpha(2D)-adrenoceptor constriction (UK-14304 plus prazosin); the half-maximum inhibitory concentration for acidosis was 7.1 and for P-O2 was 24 mmHg. alpha(1D)-Adrenoceptor constriction by the respective full and partial alpha(1D)-agonists, phenylephrine (PE) and St-587 (both plus rauwolscine), was unaffected. Because St-587 but not PE constriction was dependent on VOC activation, the sensitivity of alpha(2D)- but not alpha(1D)-constriction to acidosis and hypoxia appeared to be independent of reliance on VOCs. This was examined directly; contractile sensitivity to KCI and the VOC agonist, SDZ-202-791, was unaffected by pH 7.0 or P-O2 10 mmHg. These data suggest that alpha(2D)-constriction is sensitive to inhibition by hypoxia and acidosis through a mechanism that does not involve direct blockade of Ca2+ channels.