Oestrogen and progesterone inhibit the stimulated production of endothelin-1

Morey, Katherine; Razandi, Mahnaz; Pedram, Ali; Hu, Renming; Prins, A. Bruce; Levin, Randy

doi:10.1042/bj3301097

Cited by 119 publications

(81 citation statements)

References 52 publications

(54 reference statements)

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“…Thirdly, in vivo studies have demonstrated that oestrogen inhibited adverse vascular smooth cell remodelling (Chen et al, 1996). Concomitant with these latter e ects, the treatment of endothelial cells with oestrogen, as well as progesterone abrogated the expression of the vasoconstrictor/ proliferative peptide endothelin-1 (Morey et al, 1998). Consistent with this latter ®nding, endothelin-1 plasma levels were reported increased in post-menopausal women (Wilcox et al, 1997).…”

Section: Introductionmentioning

confidence: 65%

“…Secondly, oestrogen increased the synthesis of the potent vasodilator prostacylin via a non-genomic action in endothelial cells (Jun et al, 1998). Concomitant with the increased synthesis of vasodilatory factors, oestrogen treatment of endothelial cells inhibited the expression of the potent vasoconstrictor/proliferative peptide endothelin-1 (Morey et al, 1998). Consequently, the decrease in circulating oestrogen following menopause would favour a vasoconstrictor dominance of vascular tone.…”

Section: Discussionmentioning

confidence: 99%

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Elevated mean arterial pressure in the ovariectomized rat was normalized by ET_A receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis

Mercier

Pham-Dang

Clement

et al. 2002

British J Pharmacology

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1 The in¯uence of menopause on ventricular function and remodelling remains unde®ned. The following study examined the e ect of ovariectomy on ventricular contractility, cardiac hypertrophy and extracellular matrix protein expression. 2 Elevated circulating levels of the vasoconstrictor endothelin-1 have been reported in postmenopausal women. Moreover, endothelin-1 has been shown to in¯uence blood pressure, ventricular function and cardiac remodelling. In this regard, the potential pathophysiological role of endothelin-1 in the ovariectomized rat was assessed via the administration of the selective endothelin A receptor (ET A ) antagonist BMS-182874.3 In 3 and 6 week ovariectomized female Sprague ± Dawley rats, uterus atrophy was associated with a signi®cant increase in mean arterial pressure, and left ventricular systolic pressure, as compared to sham. By contrast, right ventricular contractile indices were normal in the ovariectomized rat. Despite increased systolic load, left ventricular hypertrophy was not evident, prepro-atrial natriuretic peptide (prepro-ANP) mRNA levels and collagen protein content were similar to sham. 4 The treatment of ovariectomized rats with BMS-182874 (60 mg kg 71 per day) did not reverse uterus atrophy. However, BMS-182874 normalized mean arterial pressure, and left ventricular systolic pressure in the ovariectomized rat. 5 Thus, despite elevated blood pressure, ovariectomized rats were not associated with either cardiac hypertrophy or ®brosis. Lastly, endothelin-1, acting via the stimulation of the ET A receptor represents an integral mechanism implicated in the increase of mean arterial pressure following ovariectomy.

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Section: Introductionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Elevated mean arterial pressure in the ovariectomized rat was normalized by ET_A receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis

Mercier

Pham-Dang

Clement

et al. 2002

British J Pharmacology

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“…Progesterone was shown to inhibit ET-1 gene expression in endothelial cells (Morey et al 1998), therefore the increment in ppET-1 during culture could represent an alleviation from the high progesterone milieu prevailing in the corpus luteum. If ET-1 peptide is concomitantly elevated, it may cause the reduction of ECE-1 levels as observed previously for luteal regression -when high levels of ET-1 are present, ECE-1 levels decrease .…”

Section: Discussionmentioning

confidence: 99%

Characterization of endothelin-1 and nitric oxide generating systems in corpus luteum-derived endothelial cells

Klipper

Gilboa²,

Levy³

et al. 2004

Reproduction

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Endothelium-derived endothelin-1 (ET-1) and nitric oxide (NO) are pivotal regulators of corpus luteum (CL) function. To have a better insight into their synthesis and action, members of the ET system (ET-1, ET converting enzyme (ECE-1) isoforms a -d, ET A and ET B receptors) along with NO synthase (NOS) isoforms -endothelial (e)NOS and inducible (i)NOS -were quantified in CL-derived endothelial cells (CLEC). The expression of these genes in microvascular CLEC, obtained by lectin-coated magnetic beads, was compared with cells removed from the luteal microenvironment and maintained in culture for different durations, and with endothelial cells (EC) derived from a large blood vessel (i.e. bovine aortic endothelial cells, BAEC). The profile of gene expression in the different EC types was determined by quantitative real-time PCR. Freshly isolated EC from mid-cycle CL exhibited high ET-1 receptor expression (both ET A and ET B ), low ET-1 synthesizing ability (both prepro (pp) ET-1 and ECE-1), but elevated iNOS -the high throughput NOS isoform. The distinct phenotype of CLEC was lost soon after an overnight culture. ET A and ET B receptor levels declined, ppET-1 levels increased while iNOS was reduced. These changes were extenuated during long-term culture of CLEC. The general pattern of gene expression in BAEC and long-term cultured CLEC was similar yet some differences, reminiscent of freshly isolated CLEC, remained: ECE-1c, ET B receptor and NOS isoforms were expressed differently in BAEC as compared with lines of CLEC. This study suggests that the luteal microenvironment is necessary to sustain the selective phenotype of its resident endothelial cells. The inverse relationship between ppET-1 and iNOS observed in freshly isolated CLEC and in cultured cells is physiologically significant and suggests that ET-1 and NO may modulate the production of each other.

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“…15,16 Endogenous inhibitors of ET-1 synthesis include nitric oxide, prostacyclin, atrial natriuretic peptides, and estrogens. [17][18][19][20] ET-1 exerts its major vascular effects through activation of 2 distinct G protein coupled ET A and ET B receptors. ET A receptors are found in the medial smooth muscle layers of the blood vessels, and atrial and ventricular myocardium.…”

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confidence: 99%

Endothelin Receptor Blockers in Cardiovascular Disease

Rich¹,

McLaughlin²

2003

Circulation

201

126

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Abstract-The endothelin (ET) system is comprised of 4 active ETs, with ET-1 being the predominant isoform in the cardiovascular system. Because of the potent vasoconstricting and mitogenic effects of ET-1 and its involvement in various cardiovascular diseases, blockade of the ET receptor has received considerable attention. ET receptor antagonism has been demonstrated to be beneficial in patients with pulmonary hypertension. The nonselective ET receptor antagonist bosentan improves exercise capacity and increases time to clinical worsening in patients with pulmonary arterial hypertension. Key Words: endothelin Ⅲ heart failure Ⅲ pulmonary heart disease T he endothelin (ET) system, like other vascular regulatory systems, consists of a parent peptide that undergoes enzymatic activation and exerts its biologic effects by modulating specific receptors. Of the 4 active ETs (ET 1 through 4), ET-1 is the predominant isoform in the cardiovascular system, which is generated through the cleavage of prepro ET-1 to big ET-1 and then to ET-1 by the action of ET-converting enzymes. ET-1 is found in endothelial cells and is released toward the vascular smooth muscle consistent with a paracrine role, but it is also produced by smooth muscle cells and cardiomyocytes. 1,2 ET-1 has vasoconstrictive and mitogenic effects, stimulates the production of growth factors such as vascular endothelial growth factor and basic fibroblast growth factor, and potentiates the effects of transforming growth factor-␤ and platelet-derived growth factor. 3-7 Chronic ET-1 stimulation can result in myocardial fibrosis and hypertrophy and vascular fibrosis with extracellular matrix proliferation. 8 In the lung, ET-1 is abundantly expressed in the pulmonary vasculature and appears to play an important role in the regulation of pulmonary vascular tone. 9 ET-1 is also produced in leukocytes where it influences the production of a wide range of cytokines in the inflammatory response. 10 ET is regulated in an autocrine fashion by physiochemical factors such as blood flow, pulsatile stretch, sheer stress, and pH. 11-13 Acute hypoxia leads to selective stimulation of the ET-1 gene and ET synthesis in the pulmonary vasculature. 14 ET-1 biosynthesis is also stimulated by low-density lipoprotein cholesterol and glucose, and thrombin. 15,16 Endogenous inhibitors of ET-1 synthesis include nitric oxide, prostacyclin, atrial natriuretic peptides, and estrogens. [17][18][19][20] ET-1 exerts its major vascular effects through activation of 2 distinct G protein coupled ET A and ET B receptors. ET A receptors are found in the medial smooth muscle layers of the blood vessels, and atrial and ventricular myocardium. 21 When stimulated, the ET A receptors induce vasoconstriction and cellular proliferation by increasing intracellular calcium.ET B receptors are localized on endothelial cells and, to some extent, smooth muscle cells and macrophages. 22 The activation of ET B receptors stimulates the release of nitric oxide and prostacyclin and prevents apoptosis. 23 Normally, t...

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Oestrogen and progesterone inhibit the stimulated production of endothelin-1

Cited by 119 publications

References 52 publications

Elevated mean arterial pressure in the ovariectomized rat was normalized by ET_A receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis

Elevated mean arterial pressure in the ovariectomized rat was normalized by ET_A receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis

Characterization of endothelin-1 and nitric oxide generating systems in corpus luteum-derived endothelial cells

Endothelin Receptor Blockers in Cardiovascular Disease

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Oestrogen and progesterone inhibit the stimulated production of endothelin-1

Cited by 119 publications

References 52 publications

Elevated mean arterial pressure in the ovariectomized rat was normalized by ETA receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis

Elevated mean arterial pressure in the ovariectomized rat was normalized by ETA receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis

Characterization of endothelin-1 and nitric oxide generating systems in corpus luteum-derived endothelial cells

Endothelin Receptor Blockers in Cardiovascular Disease

Contact Info

Product

Resources

About

Elevated mean arterial pressure in the ovariectomized rat was normalized by ET_A receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis

Elevated mean arterial pressure in the ovariectomized rat was normalized by ET_A receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis