title: Angiotensin II stimulates sodium-dependent proton extrusion in perfused ferret heart.
abstract: The Na+/H+ antiport and Na(+)-HCO3- coinflux carrier contribute to recovery from intracellular acidosis in cardiac tissue. The effects of angiotensin II (10(-12)-10(-6) M) on H+ fluxes after intracellular acid loading and during reperfusion after myocardial ischemia have been investigated in the isovolumic, Langendorff-perfused ferret heart. Intracellular pH (pHi) was estimated using 31P nuclear magnetic resonance (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 of H+ efflux consistent with stimulation of the Na+/H+ antiport. Half-maximal stimulation of H+ efflux occurred at approximately 10(-9) M, which is close to the dissociation constant of the cardiac angiotensin AT1 receptor. Stimulation via this receptor was confirmed with the nonpeptide AT1 receptor blocker, GR-117289. Angiotensin II had less pronounced effects on HCO3(-)-dependent pHi recovery after acid loading with no effect on pHi recovery after intracellular alkalosis. During reperfusion, angiotensin II significantly increased H+ extrusion but impaired contractile recovery. The results support the hypothesis that angiotensin II facilitates H+ extrusion in the heart. This may help maintain physiological homeostasis, but the hypothesized obligated Na+ influx could exacerbate cellular dysfunction during reperfusion.
authors.affiliation: Department of Biochemistry, University of Cambridge, United Kingdom.
authors.forename: A A
authors.initials: AA
authors.lastname: Grace
authors.forename: J C
authors.initials: JC
authors.lastname: Metcalfe
authors.forename: P L
authors.initials: PL
authors.lastname: Weissberg
authors.forename: H W
authors.initials: HW
authors.lastname: Bethell
authors.forename: J I
authors.initials: JI
authors.lastname: Vandenberg
mesh_terms: D000471:Alkalosis / Q000378:metabolism; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D005260:Female; D005289:Ferrets; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011312:Pressure; D011522:Protons; D012964:Sodium / Q000502:physiology*; D016277:Ventricular Function, Left
chemical_list: D001639:Bicarbonates; D011522:Protons; D000804:Angiotensin II; D000584:Amiloride; D012964:Sodium; C039614:ethylisopropylamiloride