Chronic Estrogen Treatment Increases Levels of Endothelial Nitric Oxide Synthase Protein in Rat Cerebral Microvessels

McNeill, Anne Marie; Kim, Nancy; Duckles, Sue Piper; Krause, Diana N.

doi:10.1161/01.str.30.10.2186

Cited by 154 publications

(141 citation statements)

References 23 publications

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“…However, other studies noted that the effects of 17β-estradiol on vessels display 'regional heterogeneity effects' (Tatchum-Talom et al, 2002). Explanations regarding the protective effects of 17β-estradiol have been offered by several authors on the basis of the NO or NOS-dependent pathway (Beyer et al, 2001;Geary et al, 2000;McNeill et al, 1999) and Ca 2+ transport mechanisms (Crews et al, 1999;Murphy et al, 2000;Tep-areenan et al, 2003). Consequently, we hypothesized that the effects of 17β-estradiol may influence several pathways of the contractile system in vascular smooth muscle.…”

Section: Discussionmentioning

confidence: 95%

Characteristics of contractile activity in the renal artery of ovariectomized rats

Enkhjargal

Hashimoto

Kinoshita

et al. 2008

J. Smooth Muscle Res.

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The incidence of cardiovascular disease is markedly lower in cycling, pre-menopausal women and post-menopausal women receiving estrogen than in men or untreated postmenopausal women. Clinical studies demonstrate a protective role of estrogen in hormone replacement therapy in terms of reducing cardiovascular risk. However, the benefits of hormone replacement therapy in cardiovascular disease remain unclear. We investigated the effects of estrogen on the contractile responses of the renal artery of ovariectomized Wistar rats (OVX) compared to both ovariectomized 17β-estradiol-treated rats (OVXE) and sham-operated (control) rats. Isometric contraction of renal artery was recorded with a strain gauge transducer. The maximum contractile response of the renal artery smooth muscle to KCl (80 mM) in the OVXE group was significantly higher than that in both the control and OVX groups. The phenylephrine (PE) concentration-response curves in all three groups indicated a greater sensitivity at lower concentrations of PE following treatment with 100 µM L-arginine methyl ester (L-NAME). The EC50 values for PE in the three groups were 2 times lower in the presence of L-NAME than those lacking exposure to L-NAME. The EC50 value for PE in the OVX group was ~3 times lower in the presence of L-NAME than in those lacking exposure to L-NAME and 100 nM BMY 7378, an α1D-adrenoceptor antagonist. The rate of relaxation of the PE-induced contraction (T1/2) was significantly reduced in the OVX group relative to both the control and OVXE groups.T1/2 values after treatment with 100 µM L-NAME were slower than those lacking exposure to L-NAME in all groups. Further, the T1/2 value of the OVX group was 2 times greater than that of the control; this change was reversed in the OVXE group. In conclusion, our results suggest that estrogen regulates contraction and relaxation in the renal artery via NO synthase activity and alteration of the Ca 2+ transport systems.

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Section: Discussionmentioning

confidence: 95%

Characteristics of contractile activity in the renal artery of ovariectomized rats

Enkhjargal

Hashimoto

Kinoshita

et al. 2008

J. Smooth Muscle Res.

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“…In regards to the influence of androgens on eNOS expression, increase (Simoncini et al 2003), decrease (Chatrath et al 2003) or no change (McNeill et al 1999) have all been reported. We found that aortic eNOS expression was not modified by orchidectomy as has been observed in rat mesenteric artery (Blanco-Rivero et al 2006), but in contrast to observations of nNOS expression in rat mesenteric artery , thus indicating that endogenous male sex hormones act differently, depending on tissue and target protein.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, increase (Simoncini et al 2003), decrease (Chatrath et al 2003) or no change (McNeill et al 1999) of eNOS expression by androgenic derivatives have all been described. Likewise, increase (Liu & Dillon 2002, Simoncini et al 2003 or decrease of eNOS activity by androgens has both been reported.…”

Section: Introductionmentioning

confidence: 99%

Orchidectomy increases expression and activity of Cu/Zn-superoxide dismutase, while decreasing endothelial nitric oxide bioavailability

Blanco-Rivero¹,

Sagredo²,

Balfagón³

et al. 2006

Journal of Endocrinology

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This study examines the effect of male sex hormones on the release, metabolism and function of endothelial nitric oxide (eNO) in rat aorta. Aortic segments from orchidectomized and control male Sprague-Dawley rats were used to measure eNO synthase (eNOS) expression, nitric oxide (NO) release, acetylcholine (ACh)-and sodium nitroprusside (SNP)-induced relaxation and Cu/Zn-superoxide dismutase (SOD) expression and activity. eNOS expression as well as basal and ACh-induced NO release were similar in arteries from both groups of rats. Basal superoxide anion production was similar in arteries from both groups, while ACh-induced superoxide anion formation was greater in arteries from orchidectomized than control rats. Orchidectomy increased the vasodilator effect induced by ACh, but did not alter that induced by SNP. SOD, a superoxide anion scavenger, did not modify the SNP-induced relaxation in aortas from control or orchidectomized rats. The membrane-permeable mimetic of SOD, tempol, increased the SNP-induced relaxation more in aortas from orchidectomized than control rats. The effect of endogenous SOD inhibitor, diethyl-dithiocarbamate, reduced the relaxation induced by SNP in segments from both groups of rats. The expression and activity of Cu/Zn-SOD were greater in aortas from orchidectomized than control rats. These data show that endogenous male sex hormone deprivation altered neither eNOS expression nor eNO release, while it increased the expression and activity of Cu/Zn-SOD. However, the predominant vascular effect of orchidectomy is to increase NO metabolism.

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“…Data from the Women's Health Initiative suggest that estrogen replacement can increase risk for stroke (Wassertheil-Smoller et al, 2003), but definitive effects on recovery from stroke have yet to be established. The vasorelaxant properties of estrogen have been well studied in most vascular beds, including cerebral vessels (Geary et al, 2000;Pelligrino et al, 2000;Ospina et al, 2003), and are likely orchestrated via cyclooxygenase-1 induction of prostacyclin (Ospina et al, 2002) and/or by enhanced synthesis of nitric oxide (Geary et al, 2000;McNeill et al, 1999). Recent findings in humans indicate that increasing 17b-estradiol (E2) levels amplifies cerebral blood flow (CBF) (Slopien et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Estrogen Restores Postischemic Sensitivity to the Thromboxane Mimetic U46619 in Rat Pial Artery

Qin

Hurn

Littleton-Kearney

2005

J Cereb Blood Flow Metab

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The objectives of the study were to (1) characterize the dose-response relationship to the TXA 2 analog, U46619 (0.01, 0.1, and 1 lmol/L) after global cerebral ischemia, (2) determine whether chronic 17b-estradiol (E2) replacement alters this relationship, and (3) determine if E2's mechanisms are transduced through cognate estrogen receptors. Rats were assigned to five groups (n ¼ 6): placeboimplanted ovariectomized (OVX) females, OVX plus chronic E2 (CE), OVX plus acute E2 (AE), OVX plus chronic E2 plus the estrogen receptor inhibitor ICI 182,780 (CEI), and OVX plus acute E2 plus ICI 182,780 (AEI). Rats were anesthetized, intubated, cannulated (femoral artery and vein), fitted with a closed cranial window, and subjected to 15-min reversible forebrain ischemia (4-vessel occlusion, 4-VO) and 60 mins of reperfusion. Arterial blood gases, intrawindow pressure, and temperature were controlled. Vessel diameter was measured before and 5 mins after superfusion of each concentration of U46619. Compared with preischemic responses, contractile response to U46619 was depressed at all concentrations after ischemia in the OVX group. In the chronic E2 and acute E2 groups, contractile response to 1 lmol/L of U46619 was normalized to near baseline values. However, in the CEI and the AEI groups, postischemic vasoconstriction was similar to that observed in the OVX rats. We conclude that E2 targets the cerebral microvasculature to preserve postischemic pial artery reactivity and that the effect is receptor mediated. Restoration of normal constriction to vascular agonists may be an important mechanism by which E2 protects the vasculature and diminishes tissue damage after ischemia.

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Chronic Estrogen Treatment Increases Levels of Endothelial Nitric Oxide Synthase Protein in Rat Cerebral Microvessels

Cited by 154 publications

References 23 publications

Characteristics of contractile activity in the renal artery of ovariectomized rats

Characteristics of contractile activity in the renal artery of ovariectomized rats

Orchidectomy increases expression and activity of Cu/Zn-superoxide dismutase, while decreasing endothelial nitric oxide bioavailability

Estrogen Restores Postischemic Sensitivity to the Thromboxane Mimetic U46619 in Rat Pial Artery

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