title: Protective effects of 17beta-estradiol on post-ischemic cardiac dysfunction and norepinephrine overflow through the non-genomic estrogen receptor/nitric oxide-mediated pathway in the rat heart.
abstract: The present study was undertaken to examine the effect of acute treatment with 17β-estradiol on post-ischemic cardiac dysfunction and norepinephrine overflow and its possible mechanisms. Male rat hearts were perfused with the Langendorff method and subjected to 40 min of global ischemia followed by 30 min of reperfusion. Each drug was perfused from 15 min before ischemia to 5 min after reperfusion. During reperfusion, 17β-estradiol treatment showed significantly greater functional recovery of left ventricular developed pressure (LVDP), left ventricular end diastolic pressure (LVEDP), and dP/dt(max). Excessive norepinephrine release in coronary effluent from the post-ischemic heart was notably suppressed by treatment with 17β-estradiol. These beneficial effects of 17β-estradiol were not observed in the presence of the nitric oxide synthase inhibitor N(G)-nitro-l-arginine and estrogen receptor antagonist ICI 182,780 ((7α, 17β)-7-[9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol), respectively. When NO(2)/NO(3) levels in coronary effluents after the onset of reperfusion were measured, reverse-correlation relationships between NO(2)/NO(3) production and ischemia/reperfusion-induced cardiac dysfunction, as well as norepinephrine overflow were observed. These findings suggest that 17β-estradiol exerts cardioprotective effects against ischemia/reperfusion-induced cardiac dysfunction, at least in part, by suppressing norepinephrine overflow, and that nitric oxide production via estrogen receptor activation plays a key role in this process.
authors.affiliation: Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Fukumoto
authors.forename: Masashi
authors.initials: M
authors.lastname: Tawa
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamashita
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ohkita
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D011960:Receptors, Estrogen; D009569:Nitric Oxide; D004958:Estradiol; D009638:Norepinephrine