Angiotensin II stimulates sodium-hydrogen exchange in adult rabbit ventricular myocytes.
OBJECTIVE
The aim was to characterise the effects of angiotensin II on Na+/H+ exchange in adult ventricular myocytes.


METHODS
Intracellular pH (pHi) was continuously measured with the fluorescent pH indicator, SNARF-1, in single resting myocytes obtained from adult rabbits by enzymatic dissociation. In some experiments cells were electrically paced to elicit contractions. All experiments were performed at 36 degrees C in HEPES buffered solution containing no added CO2 or HCO3- (pHo 7.4).


RESULTS
Rapid application of angiotensin II caused pHi to rise. The initial rate of rise and initial net H+ efflux responded to angiotensin II in a concentration dependent manner, EC50 = 7.8. Buffering of cytosolic calcium with the calcium chelator BAPTA did not affect the initial net H+ efflux elicited by 1 microM angiotensin II. The increase in steady state pHi was blocked by inhibitors of Na+/H+ exchange, amiloride (1 mM) and EIPA (10 microM). Angiotensin II also increased the rate of pHi recovery from intracellular acidosis at pHi values above approximately 6.9. During inhibition of Na+/H+ exchange the application of angiotensin II decreased steady state pHi. This acidosis was blocked by preincubation in dextrose-free solution containing 20.0 mM 2-deoxy-D-glucose and 10 microM EIPA. The positive inotropic effect of angiotensin II was markedly suppressed by amiloride.


CONCLUSIONS
Angiotensin II exerts a concentration dependent stimulatory effect on Na+/H+ exchange in adult rabbit ventricular myocytes. This effect does not appear to involve changes in cytosolic calcium. During inhibition of Na+/H+ exchange, angiotensin II causes pHi to fall, perhaps by stimulating metabolic acid production. The positive inotropic action of angiotensin II depends, in part, on stimulation of Na+/H+ exchange.
Matsui
H
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Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah School of Medicine, Salt Lake City, USA.
Barry
W H
WH
Livsey
C
C
Spitzer
K W
KW
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001578:Benzopyrans; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects*; D013268:Stimulation, Chemical
D000889:Anti-Arrhythmia Agents; D001578:Benzopyrans; D005456:Fluorescent Dyes; C063917:SNARF dye; D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II; D000584:Amiloride; D002118:Calcium; C039614:ethylisopropylamiloride