Role of A1 adenosine receptors in regulation of vascular tone

Huda E. Tawfik, J. Schnermann, Peter J Oldenburg, S. Janial Mustafa

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The vascular response to adenosine and its analogs is mediated by four adenosine receptors (ARs), namely, A1, A2A, A 2B, and A3. A2AARs and/or A2BARs are involved in adenosine-mediated vascular relaxation of coronary and aortic beds. However, the role of A1ARs in the regulation of vascular tone is less well substantiated. The aim of this study was to determine the role of A1ARs in adenosine-mediated regulation of vascular tone. A 1AR-knockout [A1AR(-/-)] mice and available pharmacological tools were used to elucidate the function of A1ARs and the impact of these receptors on the regulation of vascular tone. Isolated aortic rings from A1AR(-/-) and wild-type [A 1AR(+/+)] mice were precontracted with phenylephrine, and concentration-response curves for adenosine and its analogs, 5′-N-ethyl-carboxamidoadenosine (NECA, nonselective), 2-chloro-A 6-cyclopentyladenosine (CCPA, A1AR selective), 2-(2-carboxyethyl)phenethyl amino-5′-N-ethylcarboxamido-adenosine (CGS-21680, A2A selective), and 2-chloro-N6-3- obenzyladenosine-5′-N-methyluronamide (Cl-IBMECA, A3 selective) were obtained to determine relaxation. Adenosine and NECA (0.1 μM) caused small contractions of 13.9 ± 3.0 and 16.4 ± 6.4%, respectively, and CCPA at 0.1 and 1.0 μM caused contractions of 30.8 ± 4.3 and 28.1 ± 3.9%, respectively, in A1AR(+/+) rings. NECA- and CCPA-induced contractions were eliminated by 100 nM of 1,3-dipropyl-8- cyclopentylxanthine (DPCPX, selective A1AR antagonist). Adenosine, NECA, and CGS-21680 produced an increase in maximal relaxation in A 1AR(-/-) compared with A1AR(+/+) rings, whereas Cl-IBMECA did not produce contraction in either A 1AR(+/+) or A1A1R(-/-) rings. CCPA-induced contraction at 1.0 μM was eliminated by the PLC inhibitor U-73122. These data suggest that activation of A1ARs causes contraction of vascular smooth muscle through PLC pathways and negatively modulates the vascular relaxation mediated by other adenosine receptor subtypes.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number3 57-3
DOIs
StatePublished - Mar 1 2005

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Adenosine A1 Receptors
Adenosine
Blood Vessels
Adenosine-5'-(N-ethylcarboxamide)
Purinergic P1 Receptors
Phenylephrine
Vascular Smooth Muscle
Knockout Mice
Pharmacology

Keywords

  • A adenosine receptor
  • Knockout mice
  • Smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Role of A1 adenosine receptors in regulation of vascular tone. / Tawfik, Huda E.; Schnermann, J.; Oldenburg, Peter J; Mustafa, S. Janial.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 288, No. 3 57-3, 01.03.2005.

Research output: Contribution to journalArticle

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