ANGIOTENSIN-II STIMULATES SODIUM-HYDROGEN EXCHANGE IN ADULT-RABBIT VENTRICULAR MYOCYTES

Objective: The aim was to characterise the effects of angiotensin II o n Na+/H+ exchange in adult ventricular myocytes, Methods: Intracellula r pH (pH(i)) was continuously measured with the fluorescent pH indicat or, SNARF-1, in single resting myocytes obtained from adult rabbits by enzymatic dissociation. In some experiments cells were electrically p aced to elicit contractions. All experiments were performed at 36 degr ees C in HEPES buffered solution containing no added CO2 or HCO3- (pH( 0) 7.4). Results: Rapid application of angiotensin II caused pH(i) to rise. The initial rate of rise and initial net H+ efflux responded to angiotensin II in a concentration dependent manner, EC(50)=7.8. Buffer ing of cytosolic calcium with the calcium chelator BAPTA did not affec t the initial net H+ efflux elicited by 1 mu M angiotensin II. The inc rease in steady state pH(i) was blocked by inhibitors of Na+/H+ exchan ge, amiloride (1 mM) and EIPA (10 mu M). Angiotensin II also increased the rate of pH(i) recovery from intracellular acidosis at pH(i) value s above approximately 6.9, During inhibition of Na+/H+ exchange the ap plication of angiotensin II decreased steady state pH(i);. This acidos is was blocked by preincubation in dextrose-free solution containing 2 0.0 mM 2-deoxy-D-glucose and 10 mu M EIPA. The positive inotropic effe ct of angiotensin II was markedly suppressed by amiloride, Conclusions : Angiotensin II exerts a concentration dependent stimulatory effect o n Na+/H+ exchange in adult rabbit ventricular myocytes. This effect do es not appear to involve changes in cytosolic calcium, During inhibiti on of Na+/H+ exchange, angiotensin II causes pH(i) to fall, perhaps by stimulating metabolic acid production. The positive inotropic action of angiotensin II depends, in part, on stimulation of Na+/H+ exchange.