Title

Adenosine A2A Receptor Modulation of Juvenile Female Rat Skeletal Muscle Microvessel Permeability

Abstract

Little is known of the regulation of skeletal muscle microvascular exchange under resting or stimulating conditions. Adenosine (ADO) levels in skeletal muscle increase during physiological (exercise) and pathological (hypoxia, inflammation, and ischemia) conditions. Later stages of these pathologies are characterized by the loss of vascular barrier integrity. This study focused on determining which ADO receptor mediates the robust reduction in microvessel permeability to rat serum albumin (PsRSA) observed in juvenile female rats. In microvessels isolated from abdominal skeletal muscle, ADO suffusion induced a concentration-dependent reduction in arteriolar [log(IC50) = -9.8 ± 0.2 M] and venular [log(IC50) = -8.4 ± 0.2 M] PsRSA. RT-PCR and immunoblot analysis demonstrated mRNA and protein expression of ADO A1, A 2A, A2B, and A3 receptors in both vessel types, and immunofluorescence assay revealed expression of the four subtype receptors in the microvascular walls (endothelium and smooth muscle). PsRSA responses of arterioles and venules to ADO were blocked by 8-(p-sulphophenyl)theophylline, a nonselective A1 and A2 antagonist. An A2A agonist, CGS21680, was more potent than the A 1 agonist, cyclopentyladenosine, or the most-selective A2B agonist, 5′-(N-ethylcarboxamido)adenosine. The ability of CGS21680 or ADO to reduce PsRSA was abolished by the A2A antagonist, ZM241385. An adenylyl cyclase inhibitor, SQ22536, blocked the permeability response to ADO. In aggregate, these results demonstrate that, in juvenile females (before the production of the reproductive hormones), ADO enhances skeletal muscle arteriole and venule barrier function predominantly via A2A receptors using activation of adenylyl cyclase-signaling mechanisms. Copyright © 2006 the American Physiological Society.

Document Type

Article

DOI

https://doi.org/10.1152/ajpheart.00526.2006

Keywords

adenosine receptors, albumin, arteriole, microvascular exchange, venule

Publication Date

12-18-2006

Journal Title

American Journal of Physiology - Heart and Circulatory Physiology

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