Angiotensin II stimulates sodium-hydrogen exchange in adult rabbit ventricular myocytes

• Published in: Cardiovascular research 1995-02, Vol.29 (2), p.215-221
• Main Authors: MATSUI, H, BARRY, W. H, LIVSEY, C, SPITZER, K. W
• Format: Article
• Language: English
• Subjects: Amiloride - analogs & derivatives; Amiloride - pharmacology; Angiotensin II - pharmacology; Animals; Anti-Arrhythmia Agents - pharmacology; Benzopyrans; Biological and medical sciences; Calcium - metabolism; Cardiovascular system; Cells, Cultured; Cytosol - metabolism; Dose-Response Relationship, Drug; Electric Stimulation; Fluorescent Dyes; Hydrogen-Ion Concentration; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Myocardium - cytology; Myocardium - metabolism; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Rabbits; Sodium-Hydrogen Exchangers - drug effects; Stimulation, Chemical
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/0008-6363(96)88573-7

The aim was to characterise the effects of angiotensin II on Na+/H+ exchange in adult ventricular myocytes. 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). 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. 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.