APPS November 2002 Meeting Abstract 2444

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 µM) 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 µM) had no significant effect on NHE1 activity (n=5). A II (2 µM) 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.