Gender and transcriptional regulation of NO synthase and ET-1 in porcine aortic endothelial cells

Wang, Xiaofang; Barber, Dustan A.; Lewis, Daniel C.; McGregor, Christopher G.A.; Sieck, Gary C.; Fitzpatrick, Lorraine A.; Miller, Virginia M.

doi:10.1152/ajpheart.1997.273.4.h1962

Cited by 48 publications

(57 citation statements)

References 27 publications

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“…Estrogen suppresses ET-1 expression in a number of models, including humans (17,19,29,43,44). In addition, estrogen treatment of coronary artery rings reduces ET-1-mediated vasoconstriction (38).…”

Section: Discussionmentioning

confidence: 99%

Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults

Stauffer

Westby

Greiner

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Stauffer BL, Westby CM, Greiner JJ, Van Guilder GP, DeSouza CA. Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults. Am J Physiol Regul Integr Comp Physiol 298: R261-R265, 2010. First published November 25, 2009 doi:10.1152/ajpregu.00626.2009.-The prevalence of cardiovascular disease is lower in middle-aged and older women than men. Increased endothelin-1-mediated vasoconstriction has been linked to the etiology of a number of cardiovascular diseases, including atherosclerosis, heart failure, and hypertension. It is unknown whether a sex difference in endothelin-1-mediated vasoconstrictor tone exists in middle-aged and older adults. Therefore, we tested the hypothesis that middle-aged and older men would demonstrate greater ET-1-mediated vasoconstrictor tone than age-matched women. Forearm blood flow in response to intra-arterial infusions of endothelin (ET)-1, BQ-123 (a selective ET A receptor antagonist), and BQ-788 (a selective ETB receptor antagonist) was assessed by venous occlusion plethysmography in 21 women (age: 58 Ϯ 1 yr; body mass index: 26.0 Ϯ 1.0 kg/m 2 ) and 25 men (age: 57 Ϯ 2 yr; body mass index: 26.8 Ϯ 0.7 kg/m 2 ). In response to BQ-123, the increase in forearm blood flow from baseline was significantly higher in the men than the women (24 Ϯ 5% vs. 9 Ϯ 5%; P Ͻ 0.05). In contrast, the increase in forearm blood flow in response to BQ-123 coinfused with BQ-788 was greater in the women than the men, such that the maximum vasodilation to dual endothelin receptor blockade was similar between men and women (ϳ25%). There was no difference in the vasoconstrictor response to ET-1 between the sexes. These results indicate that middle-aged and older men are under greater ET A receptor-mediated vasoconstrictor tone than age-matched women. Since the ET A receptor is the predominant receptor subtype in the coronary vasculature, this sex difference in vasoconstrictor tone may be a mechanism contributing to the sex difference in the prevalence of coronary heart disease in middle-aged and older adults.endothelin-1; endothelin receptor antagonist; endothelium; vascular function; sex differences ENDOTHELIN-1 (ET-1) IS THE most abundant and important vasoconstrictor molecule released from the vasculature. Produced by the endothelium, ET-1 is predominantly released abluminally to activate ET A and ET B receptors located on the vascular smooth muscle causing smooth muscle contraction, cell proliferation, and hypertrophy (35). ET B receptors on the vascular endothelium produce vasodilation via a nitric oxide mechanism and are also a prominent clearance mechanism for circulating ET-1. ET A receptors are the predominant subtype [10 times greater number than ET B (37)] in the arterial system and the coronary arteries, in particular (30, 31, 34). Because of this disparity in receptor number, the contribution of the ET B receptor to coronary vasoregulation is limited (25). Importantly, ET-1 expression is elevated in atherosclerotic vessels (18,32), and ET-1-mediated vasoconstrict...

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Section: Discussionmentioning

confidence: 99%

Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults

Stauffer

Westby

Greiner

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The external genitalia from gonadally intact females showed changes associated with an estrus cycle. Serum levels of estrogen from gonadally intact females range from 10 to 30 pg/ml, and estrogen levels in Ovx females are below the sensitivity level of assay (6,43). Uterine weight from Ovx females was significantly lower compared with uterine weight from gonadally intact females (51.3 Ϯ 7.8 vs. 86.6 Ϯ 12.3), thus validating efficacy of the surgical interven-tion.…”

Section: Methodsmentioning

confidence: 97%

Ovariectomy increases mitogens and platelet-induced proliferation of arterial smooth muscle

Bracamonte¹,

Rud²,

Owen

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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-Experiments were designed to determine how ovariectomy modulates mitogenic factors in platelets and how these factors affect proliferation of coronary arterial smooth muscle. Platelet-derived growth factors (PDGFAB and PDGFBB), transforming growth factors (TGF-␤1 and TGF-␤2), and vascular endothelial growth factor (VEGF165) were quantified in platelet lysates and platelet-poor plasma from adult gonadally intact and ovariectomized female pigs by ELISA. Proliferation of cultured coronary arterial smooth muscle cells (SMCs) from both groups of pigs was determined in response to autologous or heterologous platelet lysates. Platelet concentrations of PDGFBB, but not PDGFAB, TGF-␤1, and TGF-␤2, increased with ovariectomy. VEGF165 was not detected in platelets from either group. Proliferation of SMCs from ovariectomized females was significantly greater on exposure to autologous or heterologous platelet lysates than proliferation of SMCs from intact females. These results indicate that ovariectomy increases concentrations of PDGFBB in platelets. Higher levels of PDGFBB in platelets in synergy with other plateletderived products could contribute to increased proliferative arterial response to injury after ovariectomy.

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“…The external genitalia from gonadally intact females showed changes associated with an estrus cycle. Serum levels of estrogen from gonadally intact females range from 10 to 30 pg/ml and estrogen levels in Ovx females are below the sensitivity level of assay (4,57). Uterine weight was used as a bioassay for the efficacy of surgery and was significantly less in Ovx females (51.3 Ϯ 7.8 g) compared with gonadally intact females (86.6 Ϯ 12.3 g).…”

Section: Animalsmentioning

confidence: 99%

Acute effects of 17β-estradiol on femoral veins from adult gonadally intact and ovariectomized female pigs

Bracamonte

Jayachandran

Rud

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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endothelium; hyperpolarizing factor; nitric oxide; potassium channels OBSERVATIONAL AND EPIDEMIOLOGICAL studies suggest that oral hormone replacement therapy provides primary prevention of coronary artery disease in postmenopausal women while it also increases the risk of venous thrombosis (5,20, 23,40,49,54,55). The reasons for these apparent opposite effects on the arterial and venous systems are not known. Effects of estrogen (17␤-estradiol) on the arterial circulation are well characterized (35). For example, 17␤-estradiol has both genomic and nongenomic effects on arteries. Some of these effects include rapid and sustained production and release of endothelium-derived nitric oxide (NO), changes in activation of K ϩ and Ca 2ϩ channels, and regulation of intracellular Ca 2ϩ (12,13,36,37,42,45,59). However, it is unknown whether 17␤-estradiol could cause effects in veins as endothelial and vascular smooth muscle cells from veins have estrogen receptors (ER)-␣ (ER␣) and -␤ (ER␤) (22). Information is needed to begin to understand mechanisms of how estrogen treatment increases the risk of venous thrombosis. Therefore, the experiments were designed to determine the acute affects of 17␤-estradiol on femoral veins and whether or not these effects were modulated by the ovarian status of the animal with the use of ovariectomy (by laparoscopy) to mimic menopause. This study fills an important gap in the literature because the acute effects of 17␤-estradiol in arteries are well documented (35), but the effects of 17␤-estradiol on veins are unknown. METHODS Animals.Gonadally intact and ovariectomized (Ovx) female Yorkshire pigs (6 mo old, 110-120 kg) were used for these experiments. The external genitalia from gonadally intact females showed changes associated with an estrus cycle. Serum levels of estrogen from gonadally intact females range from 10 to 30 pg/ml and estrogen levels in Ovx females are below the sensitivity level of assay (4, 57). Uterine weight was used as a bioassay for the efficacy of surgery and was significantly less in Ovx females (51.3 Ϯ 7.8 g) compared with gonadally intact females (86.6 Ϯ 12.3 g). All pigs were fed twice a day with Lean Grow (Land O'Lakes Farmland Feed), given free access to water, and were housed at 22°C on a 12:12-h light-dark cycle.Protocol. Four weeks after ovariectomy, Ovx and agematched gonadally intact female pigs were anesthetized (ketamine and xylazine, 12 and 8 mg/kg, respectively), and the femoral veins were removed. The veins were placed immediately into cold modified Krebs-Ringer bicarbonate solution of the following composition (in mmol/l): 118.3 NaCl, 4.7 KCl, 2.5 CaCl 2, 1.2 MgSO4, 1.2 KH2PO4, 25.0 NaHCO3, 0.026 Ca 2ϩ disodium EDTA, and 11.1 dextrose. After the adventitia was trimmed, the veins were cut into rings ϳ4-5 mm long. Some rings were stored at Ϫ80°C for subsequent Western blotting to evaluate expression of ERs. Other rings were prepared for organ chamber experiments or immunohistochemistry.Organ chamber experiments. Rings with and without endothelium were ...

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Gender and transcriptional regulation of NO synthase and ET-1 in porcine aortic endothelial cells

Cited by 48 publications

References 27 publications

Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults

Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults

Ovariectomy increases mitogens and platelet-induced proliferation of arterial smooth muscle

Acute effects of 17β-estradiol on femoral veins from adult gonadally intact and ovariectomized female pigs

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