title: Effects of angiotensin II on intracellular calcium and contracture in metabolically inhibited cardiomyocytes.
abstract: Angiotensin II (A-II) is known to potentiate ischemic dysfunction during ischemia, but the mechanisms involved are not completely established. We examined the effects of A-II on intracellular calcium concentration ([Ca++]i) and cell contracture caused by metabolic inhibition in isolated adult rabbit ventricular myocytes. [Ca++]i was assessed by flow cytometry, using the Ca(++)-sensitive fluorescent probe, fluo-3. After 90 min of exposure to 2 mM cyanide (CN) and 0 glucose, there was a significant increase in myocyte [Ca++]i. This increase was slightly augmented in the presence of 100 nM A-II. In the presence of partial Na+/K+ ATP pump inhibition ([K+]o = 0.8 mM), there was a more significant increase in [Ca++]i associated with exposure to CN + A-II vs. CN alone. Similar results were obtained with CN plus 2-deoxyglucose, and the effect of A-II was inhibited by 10 microM 5-(N-ethyl-N-isopropyl)amiloride. Myocytes exposed to 2 mM CN and 0 glucose gradually developed contracture over a 3-hr period. Addition of 100 nM A-II significantly (P < .01) enhanced loss of rod shape morphology during 3 hr of CN exposure. Partial inhibition of the Na+ pump by exposure to 0.8 mM K+ had no effect on myocyte survival in the absence of CN, but augmented the harmful effect of A-II on cell contracture caused by CN exposure. This effect of A-II was completely reversed by the addition of 1 mM amiloride, a Na+/H+ exchange inhibitor. We conclude that A-II directly enhances cell injury during CN exposure in isolated rabbit ventricular myocytes. We postulate that this effect of A-II is mediated by stimulation of Na+/H+ exchange with resultant increased [Na+]i and subsequent [Ca++]i loading, possibly via reverse Na+/Ca++ exchange.
authors.affiliation: Cardiology Division, University of Utah Medical Center, Salt Lake City, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Boston
authors.forename: T
authors.initials: T
authors.lastname: Koyama
authors.forename: J
authors.initials: J
authors.lastname: Rodriguez-Larrain
authors.forename: A
authors.initials: A
authors.lastname: Zou
authors.forename: Z
authors.initials: Z
authors.lastname: Su
authors.forename: W H
authors.initials: WH
authors.lastname: Barry
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003486:Cyanides / Q000494:pharmacology; D005434:Flow Cytometry; D006321:Heart / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000503:physiopathology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology
chemical_list: D003486:Cyanides; D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium