© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Activation of Ca2+-independent nitric oxide synthase by 17β-estradiol in post-ischemic rat heart
aDepartment of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada
bDepartment of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada
cDepartment of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada
* Corresponding author. Tel.: +1-780-492-0511; fax: +1-780-492-4325 sandy.clanachan{at}ualberta.ca
Background: Nitric oxide (NO) donors or facilitation of endogenous NO production is cardioprotective. This study sought to determine whether enhanced myocardial NO production might contribute to estrogen-induced cardioprotection. Methods: Ca2+-dependent and Ca2+-independent NOS activities (pmol min–1 mg–1 protein), NOS protein expression (quantitative immunoblot), cGMP content (pmol mg–1 protein) and LV work (Joules) were measured in hearts isolated from ovariectomized rats that were either untreated or treated chronically with 17β-estradiol (0.25 mg, 21 day release formulation). Results: After 14 days, serum levels of 17β-estradiol were 6±1 and 135±16 pg ml–1 in untreated and 17β-estradiol-treated animals, respectively. After 60 min aerobic working mode perfusion, Ca2+-dependent NOS (untreated, 1.47±0 36; 17β-estradiol 1.13±0.25) and Ca2+-independent NOS (untreated, 0.45±0.24; 17β-estradiol, 0.41±0.21) activities, eNOS and iNOS proteins and cGMP content (untreated, 0.64±0.08; 17β-estradiol, 0.76±0.12) were not different in the two groups. After 60 min low-flow (0.5 ml min–1) ischemia and 30 min reperfusion, Ca2+-dependent NOS activities were again similar (untreated, 1.25±0.23; 17β-estradiol, 0.78±0.27). However, after reperfusion, Ca2+-independent NOS activity (untreated, 0.39±0.10; 17β-estradiol, 1.36±0.36) was 3.5-fold higher (P=0.008) and cGMP content (untreated, 0.30±0.03; 17β-estradiol, 0.49±0.07) was 1.6-fold higher (P=0.017) in hearts from 17β-estradiol-treated animals. Although pre-ischemic function was similar, recovery of post-ischemic LV work was 2-fold greater (P=0.024) in the 17β-estradiol group. Conclusion: The ability of ischemia and reperfusion in combination with chronic 17β-estradiol to increase Ca2+-independent NOS activity and cGMP content supports a role for enhanced myocardial NO signaling in 17β-estradiol-induced cardioprotection.
KEYWORDS Hormones; Ischemia; Nitric oxide; Reperfusion; Ventricular function
1 Present address: Division of Cardiology, Johns Hopkins University, 720 Rutland Avenue, Ross 844, Baltimore, MD 21205, USA.
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