title: Acute effects of 17beta-estradiol on myocardial pH, Na+, and Ca2+ and ischemia-reperfusion injury.
abstract: Evidence suggests that 1) ischemia-reperfusion injury is due largely to cytosolic Ca(2+) accumulation resulting from functional coupling of Na(+)/Ca(2+) exchange (NCE) with stimulated Na(+)/H(+) exchange (NHE1) and 2) 17beta-estradiol (E2) stimulates release of NO, which inhibits NHE1. Thus we tested the hypothesis that acute E2 limits myocardial Na(+) and therefore Ca(2+) accumulation, thereby limiting ischemia-reperfusion injury. NMR was used to measure cytosolic pH (pH(i)), Na(+) (Na(i)(+)), and calcium concentration ([Ca(2+)](i)) in Krebs-Henseleit (KH)-perfused hearts from ovariectomized rats (OVX). Left ventricular developed pressure (LVDP) and lactate dehydrogenase (LDH) release were also measured. Control ischemia-reperfusion was 20 min of baseline perfusion, 40 min of global ischemia, and 40 min of reperfusion. The E2 protocol was identical, except that 1 nM E2 was included in the perfusate before ischemia and during reperfusion. E2 significantly limited the changes in pH(i), Na(i)(+), and [Ca(2+)](i) during ischemia (P < 0.05). In control OVX vs. OVX+E2, pH(i) fell from 6.93 +/- 0.03 to 5.98 +/- 0.04 vs. 6.96 +/- 0.04 to 6.68 +/- 0.07; Na(i)(+) rose from 25 +/- 6 to 109 +/- 14 meq/kg dry wt vs. 25 +/- 1 to 76 +/- 3; [Ca(2+)](i) changed from 365 +/- 69 to 1,248 +/- 180 nM vs. 293 +/- 66 to 202 +/- 64 nM. E2 also improved recovery of LVDP and diminished release of LDH during reperfusion. Effects of E2 were diminished by 1 microM N(omega)-nitro-L-arginine methyl ester. Thus the data are consistent with the hypothesis. However, E2 limitation of increases in [Ca(2+)](i) is greater than can be accounted for by the thermodynamic effect of reduced Na(i)(+) accumulation on NCE.
authors.affiliation: Department of Physiology and Membrane Biology, University of California, Davis, California 95616-8644, USA. seanderson@ucdavis.edu <seanderson@ucdavis.edu>
authors.forename: Steven E
authors.initials: SE
authors.lastname: Anderson
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Kirkland
authors.forename: Andrea
authors.initials: A
authors.lastname: Beyschau
authors.forename: Peter M
authors.initials: PM
authors.lastname: Cala
mesh_terms: D000143:Acids / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010052:Ovariectomy; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
chemical_list: D000143:Acids; D011522:Protons; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D009569:Nitric Oxide; D004958:Estradiol; D012964:Sodium; D007770:L-Lactate Dehydrogenase; D002118:Calcium