ADENOSINE INHIBITS ANGIOTENSIN II ACTIVATION OF THE CARDIAC Na+/H+ EXCHANGER IN RAT VENTRICULAR MYOCYTES
Alexander S. Nicholls, Lele Jiang, David G. Allen, Department of Physiology and Institute for Biomedical Research, University of Sydney, NSW 2006.
The cardiac Na+/H+ exchanger (NHE1) is one major pathway by which the heart extrudes protons during intracellular acidosis. Adenosine is produced by the ischemic heart and has some role in protection from ischemic damage1. Angiotensin II (A II) stimulates NHE1 activity2 while inhibition of NHE1 activity protects against ischemic damage3. Avkiran et al. recently showed that α1-adrenergic stimulation of NHE1 is inhibited by GR 79236, an adenosine A1 receptor agonist4. In the present study we tested whether adenosine inhibits A II-induced stimulation of NHE1.
Intracellular pH was measured in isolated rat ventricular myocytes and NHE1 activity was determined during recovery from NH4Cl (20 mM) prepulse. Control acid efflux was 2.36 ▒ 0.22 mM/min in a HCO3-free solution. The NHE1 inhibitor, zoniporide (2 ÁM) reduced acid efflux to 0.28 ▒ 0.027 mM/min (n=4, p<0.001) showing that most acid efflux under these conditions was carried by NHE1. Adenosine alone (10 ÁM) had no significant effect on NHE1 activity (n=5). A II (2 ÁM) increased NHE1 activity substantially to 6.46 ▒ 1.24 mM/min (n=6, p<0.00002) confirming the earlier findings2. However, in the presence of adenosine, the stimulatory effect of A II was eliminated (1.84 ▒ 0.61mM/min, n=4, p>0.3 compared to control).
These results suggest that adenosine might protect against ischemic damage by preventing an A II-induced stimulation of NHE1.
(1) Sommerschild HT, Kirkebøen KA. Acta Anaesthesiologica Scandinavica. 2000;44:1038-1055.
(2) Matsui H, Barry WH, Livsey C, Spitzer KW. Cardiovascular Research. 1995;29:215-221.
(3) Karmazyn M. American Journal of Physiology. 1988;255:H608-H615.
(4) Avkiran M, Yokoyama H. British Journal of Pharmacology. 2000;131:659-662.