Angiotensin ii stimulates sodium-dependent proton extrusion in
perfused ferret heart.
Grace, Andrew A., James C. Metcalfe, Peter L. Weissberg, Hugh W. L.
Bethell, and Jamie I. Vandenberg.
Department of Biochemistry, University of Cambridge, Tennis Court
Road, Cambridge, United Kingdom CB2 1QW
APStracts 2:0437C, 1995.
The Na+-H+ antiport and Na+-HCO3- co-influx carrier contribute to
recovery from intracellular acidosis in cardiac tissue. The effects
of angiotensin II (10-12 - 10-6 M) on proton fluxes following
intracellular acid loading, and during reperfusion after myocardial
ischemia have been investigated in the isovolumic, Langendorff
-perfused ferret heart. pHi was estimated using 31P NMR spectroscopy
from the chemical shift of intracellular deoxyglucose-6-phosphate or
inorganic phosphate. Angiotensin II produced concentration-dependent
stimulation (maximum at 10-6 M: 67%) of 5-(N-ethyl-N-isopropyl)
amiloride (EIPA)-sensitive Na+-dependent proton efflux consistent
with stimulation of the Na+-H+ antiport. Half-maximal stimulation of
proton efflux occurred at 10-9 M which is close to the K[delta] of
the cardiac AT1 receptor. Stimulation via this receptor was confirmed
using the nonpeptide AT1 receptor blocker, GR117289. Angiotensin II
had less pronounced effects on HCO3--dependent pHi recovery following
acid loading with no effect on pHi recovery following intracellular
alkalosis. During reperfusion, angiotensin II significantly increased
proton extrusion but impaired contractile recovery. The results
support the hypothesis that angiotensin II facilitates proton
extrusion in the heart. This may help maintain physiological
homeostasis but the hypothesized obligated Na+-influx could
exacerbate cellular dysfunction during reperfusion.
Received 19 September 1994; accepted in final form 30 November
1995.
APS Manuscript Number C560-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 12 December 95