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Adenosine A(3)-receptor stimulation attenuates postischemic dysfunction through K(ATP) channels.

Publication ,  Journal Article
Thourani, VH; Nakamura, M; Ronson, RS; Jordan, JE; Zhao, ZQ; Levy, JH; Szlam, F; Guyton, RA; Vinten-Johansen, J
Published in: Am J Physiol
July 1999

We tested the hypothesis that selective adenosine A(3)-receptor stimulation reduces postischemic contractile dysfunction through activation of ATP-sensitive potassium (K(ATP)) channels. Isolated, buffer-perfused rat hearts (n = 8/group) were not drug pretreated (control) or were pretreated with adenosine (20 microM), 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA; A(3) agonist, 100 nM), Cl-IB-MECA + 8-(3-noradamantyl)-1,3-dipropylxanthine (KW-3902; A(1) antagonist, 5 microM), Cl-IB-MECA + glibenclamide (Glib; K(ATP)-channel blocker, 0. 3 microM), or Glib alone for 12 min before 30 min of global normothermic ischemia followed by 2 h of reperfusion. After 2 h of reperfusion, left ventricular developed pressure (LVDP, %baseline) in control hearts was depressed to 34 +/- 2%. In hearts pretreated with Cl-IB-MECA, there was a statistically significant increase in LVDP (50 +/- 6%), which was reversed with coadministration of Glib (37 +/- 1%). Control hearts also showed similar decreases in left ventricular peak positive rate of change in pressure (dP/dt). Therefore, the A(3) agonist significantly attenuated postischemic cardiodynamic injury compared with the control, which was reversed by Glib. Cumulative creatine kinase (CK in U/min) activity was most pronounced in the control group (10.4 +/- 0.6) and was significantly decreased by Cl-IB-MECA (7.5 +/- 0.4), which was reversed by coadministration of Glib (9.4 +/- 0.2). Coronary flow was increased during adenosine infusion (160% of baseline) but not during Cl-IB-MECA infusion. Effects of Cl-IB-MECA were not reversed by the specific A(1) antagonist KW-3902. We conclude that cardioprotection afforded by A(3)-receptor stimulation may be mediated in part by K(ATP) channels. Cl-IB-MECA may be an effective pretreatment agent that attenuates postischemic cardiodynamic dysfunction and CK release without the vasodilator liability of other adenosine agonists.

Duke Scholars

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

July 1999

Volume

277

Issue

1

Start / End Page

H228 / H235

Location

United States

Related Subject Headings

  • Ventricular Function, Left
  • Receptors, Purinergic P1
  • Receptor, Adenosine A3
  • Rats, Sprague-Dawley
  • Rats
  • Potassium Channels
  • Myocardial Ischemia
  • In Vitro Techniques
  • Glyburide
  • Diastole
 

Citation

APA
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MLA
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Thourani, V. H., Nakamura, M., Ronson, R. S., Jordan, J. E., Zhao, Z. Q., Levy, J. H., … Vinten-Johansen, J. (1999). Adenosine A(3)-receptor stimulation attenuates postischemic dysfunction through K(ATP) channels. Am J Physiol, 277(1), H228–H235. https://doi.org/10.1152/ajpheart.1999.277.1.H228
Thourani, V. H., M. Nakamura, R. S. Ronson, J. E. Jordan, Z. Q. Zhao, J. H. Levy, F. Szlam, R. A. Guyton, and J. Vinten-Johansen. “Adenosine A(3)-receptor stimulation attenuates postischemic dysfunction through K(ATP) channels.Am J Physiol 277, no. 1 (July 1999): H228–35. https://doi.org/10.1152/ajpheart.1999.277.1.H228.
Thourani VH, Nakamura M, Ronson RS, Jordan JE, Zhao ZQ, Levy JH, et al. Adenosine A(3)-receptor stimulation attenuates postischemic dysfunction through K(ATP) channels. Am J Physiol. 1999 Jul;277(1):H228–35.
Thourani, V. H., et al. “Adenosine A(3)-receptor stimulation attenuates postischemic dysfunction through K(ATP) channels.Am J Physiol, vol. 277, no. 1, July 1999, pp. H228–35. Pubmed, doi:10.1152/ajpheart.1999.277.1.H228.
Thourani VH, Nakamura M, Ronson RS, Jordan JE, Zhao ZQ, Levy JH, Szlam F, Guyton RA, Vinten-Johansen J. Adenosine A(3)-receptor stimulation attenuates postischemic dysfunction through K(ATP) channels. Am J Physiol. 1999 Jul;277(1):H228–H235.

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

July 1999

Volume

277

Issue

1

Start / End Page

H228 / H235

Location

United States

Related Subject Headings

  • Ventricular Function, Left
  • Receptors, Purinergic P1
  • Receptor, Adenosine A3
  • Rats, Sprague-Dawley
  • Rats
  • Potassium Channels
  • Myocardial Ischemia
  • In Vitro Techniques
  • Glyburide
  • Diastole