Inhibition of arteriole alpha 2- but not alpha 1-adrenoceptor constriction by acidosis and hypoxia in vitro.

Abstract

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 microns control diam) were measured by videomicroscopy for bath-added agents. Decreases in pH (7.4-7.0) or PO2 (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 PO2 was 24 mmHg. alpha 1D-Adrenoceptor constriction by the respective full and partial alpha 1-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 KCl and the VOC agonist, SDZ-202-791, was unaffected by pH 7.0 or PO2 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 dihydropyridine-sensitive Ca2+ channels.

• Authors: J Tateishi, J E Faber
• Journal: The American journal of physiology (Am J Physiol) Vol. 268 Issue 5 Pt 2 Pg. H2068-76 (May 1995) ISSN: 0002-9513 [Print] United States
• PMID: 7771557 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Calcium Channel Agonists
• Calcium Channels
• Dihydropyridines
• Receptors, Adrenergic, alpha
• Potassium Chloride
• SAN 202791

Topics

• Acidosis (physiopathology)
• Animals
• Arterioles (drug effects, innervation)
• Calcium Channel Agonists (pharmacology)
• Calcium Channels (drug effects, physiology)
• Dihydropyridines (pharmacology)
• Electrophysiology
• Hypoxia (physiopathology)
• Potassium Chloride (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Adrenergic, alpha (classification, physiology)
• Vasoconstriction