ANGIOTENSIN-II STIMULATES SODIUM-DEPENDENT PROTON EXTRUSION IN PERFUSED FERRET HEART

The Na+/H+ antiport and Na+-HCO3- coinflux carrier contribute to recov ery from intracellular acidosis in cardiac tissue. The effects of angi otensin II (10(-12)-10(-6) M) on H+ fluxes after intracellular acid lo ading and during reperfusion after myocardial ischemia have been inves tigated in the isovolumic, Langendorff-perfused ferret heart. Intracel lular pH (pH(i)) was estimated using P-31 nuclear magnetic resonance ( NMR) spectroscopy from the chemical shift of intracellular deoxyglucos e-6-phosphate or inorganic phosphate. Angiotensin II produced concentr ation-dependent stimulation (maximum at 10(-6) M: 67%) of 5-(N-ethyl-N -isopropyl)amiloride (EIPA)-sensitive Na+-dependent H+ efflux consiste nt with stimulation of the Na+/H+ antiport. Half-maximal stimulation o f H+ efflux occurred at similar to 10(-9) ill, which is close to the d issociation constant of the cardiac angiotensin AT(1) receptor. Stimul ation via this receptor was confirmed with the nonpeptide AT(1) recept or blocker, GR-117289. Angiotensin II had less pronounced effects on H CO3--dependent pH(i) recovery after acid loading with no effect on pH( i) recovery after intracellular alkalosis. During reperfusion, angiote nsin II significantly increased H+ extrusion but impaired contractile recovery. The results support the hypothesis that angiotensin II facil itates H+ extrusion in the heart. This may help maintain physiological homeostasis, but the hypothesized obligated Na+ influx could exacerba te cellular dysfunction during reperfusion.