Vasodilator responses to adenosine and hyperemia are mediated by A1 and A2 receptors in the cat vascular bed

Trinity J. Bivalacqua, Hunter C. Champion, David G. Lambert, Philip J. Kadowitz

Research output: Contribution to journalArticlepeer-review

Abstract

Hemodynamic responses to adenosine, the A1 receptor agonists N6-cyclopentyladenosine (CPA) and adenosine amine congener (ADAC), and the A2 receptor agonist 5′-(N-cyclopropyl)-carboxamido-adenosine (CPCA) were investigated in the hindquarter vascular bed of the cat under constant-flow conditions. Injections of adenosine, CPA, ADAC, CPCA, ATP, and adenosine 5′-O-(3-thiotriphosphate) (ATPγS) into the perfusion circuit induced dose-related decreases in perfusion pressure. Vasodilator responses to the A1 agonists were reduced by the A1 receptor antagonists KW-3902 and CGS-15943, whereas responses to CPCA were reduced by the A2 antagonist KF-17837. Vasodilator responses to adenosine were reduced by KW-3902, CGS-15943, and by KF-17837, suggesting a role for both A1 and A2 receptors. Vasodilator responses to ATP and the nonhydrolyzable ATP analog ATPγS were not attenuated by CGS-15943 or KF-17837. After treatment with the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester, the cyclooxygenase inhibitor sodium meclofenamate, or the ATP-dependent K+ (KATP+) channel antagonists U-37883A or glibenclamide, responses to adenosine and ATP were not altered. Responses to adenosine, CPA, and CPCA were increased in duration by rolipram, a type 4 cAMP phosphodiesterase inhibitor, but were not altered by zaprinast, a type 5 cGMP phosphodiesterase inhibitor. When blood flow was interrupted for a 30-s period, the magnitude and duration of the reactive vasodilator response were reduced by A1 and A2 receptor antagonists. These data suggest that vasodilator responses to adenosine and the A1 and A2 agonists studied are not dependent on the release of cyclooxygenase products, nitric oxide, or the opening of KATP+ channels in the regional vascular bed of the cat. The present data suggest a role for cAMP in mediating responses to adenosine and suggest that vasodilator responses to adenosine and to reactive hyperemia are mediated in part by A1 and A2 receptors in the hindquarter vascular bed of the cat.

Original languageEnglish (US)
Pages (from-to)R1696-R1709
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume282
Issue number6 51-6
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • CGS-15943
  • KF-17837
  • Purinergic responses
  • Reactive vasodilation
  • Regional vascular bed

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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