17β-Estradiol stimulates expression of endothelial and inducible NO synthase in rat myocardium in-vitro and in-vivo

Nuedling, Simone; Kahlert, Stefan; Loebbert, Kerstin; Doevendans, Pieter A.; Meyer, Rainer; Vetter, Hans; Grohé, Christian

doi:10.1016/s0008-6363(99)00093-0

Cited by 175 publications

(101 citation statements)

References 32 publications

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“…It also has been well demonstrated that E2 increases activity of NOS and NO release during ischemia and reperfusion (20,39,41). Furthermore, there is good evidence that the NO donor sodium nitroprusside, as well as 8-bromoguanosine 3Ј,5Ј-cyclic monophosphate (8-BrcGMP), inhibit pH i recovery in cardiac myocytes from male rats after NH 4 Cl washout in HEPES medium (22).…”

Section: Discussionmentioning

confidence: 99%

Acute effects of 17β-estradiol on myocardial pH, Na⁺, and Ca²⁺ and ischemia-reperfusion injury

Anderson¹,

Kirkland²,

Beyschau³

et al. 2005

American Journal of Physiology-Cell Physiology

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Evidence suggests that 1) ischemia-reperfusion injury is due largely to cytosolic Ca 2ϩ accumulation resulting from functional coupling of Na ϩ /Ca 2ϩ exchange (NCE) with stimulated Na ϩ /H ϩ exchange (NHE1) and 2) 17␤-estradiol (E2) stimulates release of NO, which inhibits NHE1. Thus we tested the hypothesis that acute E2 limits myocardial Na ϩ and therefore Ca 2ϩ accumulation, thereby limiting ischemia-reperfusion injury. NMR was used to measure cytosolic pH (pHi), Na ϩ (Na i ϩ ), and calcium concentration ([Ca 2ϩ ]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 ϩ , and [Ca 2ϩ ]i during ischemia (P Ͻ 0.05). In control OVX vs. OVXϩE2, pH i fell from 6.93 Ϯ 0.03 to 5.98 Ϯ 0.04 vs. 6.96 Ϯ 0.04 to 6.68 Ϯ 0.07; Na i ϩ rose from 25 Ϯ 6 to 109 Ϯ 14 meq/kg dry wt vs. 25 Ϯ 1 to 76 Ϯ 3; [Ca 2ϩ ]i changed from 365 Ϯ 69 to 1,248 Ϯ 180 nM vs. 293 Ϯ 66 to 202 Ϯ 64 nM. E2 also improved recovery of LVDP and diminished release of LDH during reperfusion. Effects of E2 were diminished by 1 M N -nitro-L-arginine methyl ester. Thus the data are consistent with the hypothesis. However, E2 limitation of increases in [Ca 2ϩ ]i is greater than can be accounted for by the thermodynamic effect of reduced Na i ϩ accumulation on NCE. myocardial ischemia; Na ϩ /H ϩ exchange; Na ϩ /Ca 2ϩ exchange; nuclear magnetic resonance; ischemic biology; ion channels/membrane transport; transplantation IT IS CLEAR THAT OUR UNDERSTANDING of the effects of endogenous and exogenous estrogen on the cardiovascular system, and in particular on its role in modifying susceptibility to ischemic injury, is deficient. It is more important than ever that fundamental research be conducted to understand the basis for the effects of estrogen (50). Because results of various studies are inconsistent and/or difficult to interpret, we have taken a reductionist approach to testing the acute effects of exogenous 17␤-estradiol (E2) on ischemic myocardium within the context of the well-accepted paradigm that ischemic injury is largely the result of the following chain of events. Anaerobic metabolism decreases cytosolic pH (pH i ), which stimulates pHregulatory Na ϩ /H ϩ exchange (NHE1) to increase Na ϩ uptake and thereby increase intracellular Na ϩ (Na i ϩ ). Increases in (3,7,31,37,46,49). In the heart, there are questions about whether the bulk of Na ϩ and Ca 2ϩ entry occurs during ischemia or reperfusion, but there is a growing consensus that much of the Ca 2ϩ entry is Na ϩ dependent (36). Numerous studies have shown that E2 stimulates NOS activity and/or the release of nitric oxide (NO) in the heart (20,39,40) and that female hormonelinked changes in Na ϩ...

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Section: Discussionmentioning

confidence: 99%

Acute effects of 17β-estradiol on myocardial pH, Na⁺, and Ca²⁺ and ischemia-reperfusion injury

Anderson¹,

Kirkland²,

Beyschau³

et al. 2005

American Journal of Physiology-Cell Physiology

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“…Exogenous estrogen protects against atherosclerosis by modulating low-density lipoprotein oxidation, binding free radicals and lowering plasma cholesterol (6,7). Enhanced expression of endothelial nitric oxide synthase and its inducible isoform in the myocardium have also been observed with the administration of exogenous estrogen (8,9).…”

Section: Introductionmentioning

confidence: 94%

Myocardial antioxidant and oxidative stress changes due to sex hormones

Barp

Araújo

Fernandes

et al. 2002

Braz J Med Biol Res

154

116

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The purpose of the present study was to examine myocardial antioxidant and oxidative stress changes in male and female rats in the presence of physiological sex hormone concentrations and after castration. Twenty-four 9-week-old Wistar rats were divided into four groups of 6 animals each: 1) sham-operated females, 2) castrated females, 3) sham-operated males, and 4) castrated males. When testosterone and estrogen levels were measured by radioimmunoassay, significant differences were observed between the castrated and control groups (both males and females), demonstrating the success of castration. Progesterone and catalase levels did not change in any group. Control male rats had higher levels of glutathione peroxidase (50%) and lower levels of superoxide dismutase (SOD, 14%) than females. Control females presented increased levels of SOD as compared to the other groups. After castration, SOD activity decreased by 29% in the female group and by 14% in the male group as compared to their respective controls. Lipid peroxidation (LPO) was assessed to evaluate oxidative damage to cardiac membranes by two different methods, i.e., TBARS and chemiluminescence. LPO was higher in male controls compared to female controls when evaluated by both methods, TBARS (360%) and chemiluminescence (46%). Castration induced a 200% increase in myocardial damage in females as determined by TBARS and a 20% increase as determined by chemiluminescence. In males, castration did not change LPO levels. These data suggest that estrogen may have an antioxidant role in heart muscle, while testosterone does not.

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“…24 These transcription factors can activate downstream target genes such as the endothelial/inducible isoforms of NO synthase as well as connexin 43 in the heart. 25,26 In the present study, we used an in vivo, closed-chest mouse model to test the hypothesis that ER␣ and ER␤ per se influence ventricular repolarization and ventricular automaticity in a female mouse model with chronic anterior MI and studied the expression of potassium channels as molecular targets of ER␣ and ER␤ underlying these differences.…”

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confidence: 99%

Female Mice Lacking Estrogen Receptor β Display Prolonged Ventricular Repolarization and Reduced Ventricular Automaticity After Myocardial Infarction

et al. 2005

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Background-Major gender-based differences in the incidence of ventricular tachyarrhythmia after myocardial infarction have been shown in humans. Although the underlying mechanisms are unclear, earlier studies suggest that estrogen receptor-mediated effects play a major role in this process. Methods and Results-We examined the effect of estrogen receptor ␣ (ER␣) and estrogen receptor ␤ (ER␤) on the electrophysiological phenotype in female mice with and without chronic anterior myocardial infarction. There was no significant difference in overall mortality, infarct size, and parameters of left ventricular remodeling when we compared infarcted ER␣-deficient and ER␤-deficient mice with infarcted wild-type animals. In the 12-hour telemetric ECG recording 6 weeks after myocardial infarction, surface ECG parameters did not show significant differences in comparisons of ER␣-deficient mice versus wild-type controls, infarcted versus noninfarcted ER␣-deficient mice, and infarcted ER␣-deficient versus infarcted wild-type mice. However, infarcted ER␤-deficient versus noninfarcted ER␤-deficient mice showed a significant prolongation of the QT (

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17β-Estradiol stimulates expression of endothelial and inducible NO synthase in rat myocardium in-vitro and in-vivo

Abstract: Taken together, these results show that E2 stimulates the expression of iNOS/eNOS in neonatal and adult cardiomyocytes in-vivo and in-vitro. These novel findings provide a potential mechanism of how estrogen may modulate NOS expression and NO formation in the myocardium.

Cited by 175 publications

References 32 publications

Acute effects of 17β-estradiol on myocardial pH, Na⁺, and Ca²⁺ and ischemia-reperfusion injury

Acute effects of 17β-estradiol on myocardial pH, Na⁺, and Ca²⁺ and ischemia-reperfusion injury

Myocardial antioxidant and oxidative stress changes due to sex hormones

Female Mice Lacking Estrogen Receptor β Display Prolonged Ventricular Repolarization and Reduced Ventricular Automaticity After Myocardial Infarction

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17β-Estradiol stimulates expression of endothelial and inducible NO synthase in rat myocardium in-vitro and in-vivo

Abstract: Taken together, these results show that E2 stimulates the expression of iNOS/eNOS in neonatal and adult cardiomyocytes in-vivo and in-vitro. These novel findings provide a potential mechanism of how estrogen may modulate NOS expression and NO formation in the myocardium.

Cited by 175 publications

References 32 publications

Acute effects of 17β-estradiol on myocardial pH, Na+, and Ca2+ and ischemia-reperfusion injury

Acute effects of 17β-estradiol on myocardial pH, Na+, and Ca2+ and ischemia-reperfusion injury

Myocardial antioxidant and oxidative stress changes due to sex hormones

Female Mice Lacking Estrogen Receptor β Display Prolonged Ventricular Repolarization and Reduced Ventricular Automaticity After Myocardial Infarction

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Acute effects of 17β-estradiol on myocardial pH, Na⁺, and Ca²⁺ and ischemia-reperfusion injury

Acute effects of 17β-estradiol on myocardial pH, Na⁺, and Ca²⁺ and ischemia-reperfusion injury