Dilatory responses to estrogenic compounds in small femoral arteries of male and female estrogen receptor-β knockout mice

Cruz, María Natalia; Douglas, Gillian; Gustafsson, Jan Åke; Poston, Lucilla; Kublickiene, Karolina

doi:10.1152/ajpheart.00815.2005

Cited by 21 publications

(21 citation statements)

References 60 publications

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“…The rapid onset of the ER-␣-and ER-␤-mediated decrease in PA vasoconstriction (Ͻ20 min for PE-induced vasoconstriction and Ͻ45 min for HPV) is suggestive of a nongenomic increase in NO release. The concentrations required to mediate these effects were similar to those reported by other investigators demonstrating vasorelaxation in isolated systemic arteries (6,36). Nongenomic signaling by estrogens appear to be particularly important in "nontraditional" sex hormone target tissues (12).…”

Section: Discussionsupporting

confidence: 85%

Selective estrogen receptor-α and estrogen receptor-β agonists rapidly decrease pulmonary artery vasoconstriction by a nitric oxide-dependent mechanism

Lahm¹,

Crisostomo²,

Markel³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Selective estrogen receptor-␣ and estrogen receptor-␤ agonists rapidly decrease pulmonary artery vasoconstriction by a nitric oxide-dependent mechanism. Am J Physiol Regul Integr Comp Physiol 295: R1486 -R1493, 2008. First published October 1, 2008 doi:10.1152/ajpregu.90667.2008.-Both endogenous and exogenous estrogen decrease pulmonary artery (PA) vasoconstriction. Whether these effects are mediated via estrogen receptor (ER)-␣ or ER-␤, and whether the contribution of ERs is stimulus-dependent, remains unknown. We hypothesized that administration of the selective ER-␣ agonist propylpyrazole triol (PPT) and/or the selective ER-␤ agonist diarylpropiolnitrile (DPN) rapidly decreases PA vasoconstriction induced by pharmacologic and hypoxic stimuli via a nitric oxide (NO)-dependent mechanism. PA rings (n ϭ 3-10/group) from adult male Sprague-Dawley rats were suspended in physiologic organ baths. Force displacement was measured. Vasoconstrictor responses to phenylephrine (10 Ϫ8 M Ϫ 10 Ϫ5 M) and hypoxia (PO2 35-45 mmHg) were determined. Endothelium-dependent and -independent vasorelaxation were measured by generating dose-response curves to acetylcholine (10 Ϫ8 M Ϫ 10 Ϫ4 M) and sodium nitroprusside (10 Ϫ9 M Ϫ 10 Ϫ5 M). PPT or DPN (10 Ϫ9 M Ϫ 5 ϫ 10 Ϫ5 M) were added to the organ bath in the presence and absence of the NO-synthase inhibitor N -nitro-L-arginine methyl ester (L-NAME) (10 Ϫ4 M). Selective ER-␣ activation (PPT, 5 ϫ 10 Ϫ5 M) rapidly (Ͻ20 min) decreased phenylephrine-induced vasoconstriction. This effect, as well as PPT's effects on endothelium-dependent vasorelaxation, were neutralized by L-NAME. In contrast, selective ER-␤ activation (DPN, 5 ϫ 10 Ϫ5 M) rapidly decreased phase II of hypoxic pulmonary vasoconstriction (HPV). L-NAME eliminated this phenomenon. Lower PPT or DPN concentrations were less effective. We conclude that both ER-␣ and ER-␤ decrease PA vasoconstriction. The immediate onset of effect suggests a nongenomic mechanism. The contribution of specific ERs appears to be stimulus specific, with ER-␣ primarily modulating phenylephrine-induced vasoconstriction, and ER-␤ inhibiting HPV. NO inhibition eliminates these effects, suggesting a central role for NO in mediating the pulmonary vascular effects of both ER-␣ and ER-␤. propylpyrazole triol; diarylpropiolnitrile; phenylephrine; hypoxic pulmonary vasoconstriction; nongenomic effects FEMALE SEX IS INCREASINGLY recognized as a protective factor in patients suffering from trauma and sepsis (12, 16). The critical role of sex hormones has recently been recognized. In particular, 17␤-estradiol (E2) has been shown to improve outcomes in experimental trauma hemorrhage and shock (13, 14, 41), sepsis (5, 7, 12), myocardial ischemia-reperfusion (39, 40), and acute lung injury (30,35,42). The protective effects of E2 are mediated via estrogen receptor (ER)-␣ and ER-␤. The effects of these ER subtypes are tissue and compartment specific. For example, ER-␣ decreases proinflammatory cytokine production by splenic macrophages and Kupffer cells after traumahemor...

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Section: Discussionsupporting

confidence: 85%

Selective estrogen receptor-α and estrogen receptor-β agonists rapidly decrease pulmonary artery vasoconstriction by a nitric oxide-dependent mechanism

Lahm¹,

Crisostomo²,

Markel³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…Indeed, controversy exists as to whether resveratrol acts predominantly through ER␤ (27) or has mixed agonist/antagonist actions on both receptors, depending on the cell type or vascular bed studied (10). Thus, from our data and previous reports, it could be suggested that occupancy of either receptor subtypes evokes vasodilatation and that ligands with higher selectivity for one ER subtype achieve a greater biological response than those with similar affinity for both (16,35).…”

Section: Discussionmentioning

confidence: 60%

“…Each artery was mounted as an isometric preparation on stainless steel wires (diameter, 40 m) attached to a force transducer and a micrometer, respectively, as described previously (16,34). Commercially available software was used for calibrations and for data collection (Myodac, version 2.1, Danish Myo Technology).…”

Section: Patients Populationmentioning

confidence: 99%

Acute responses to phytoestrogens in small arteries from men with coronary heart disease

Cruz¹,

Luksha²,

Henareh³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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The aim of this study was to investigate acute vasodilator responses to phytoestrogens and selective estrogen receptor-alpha (ERalpha) agonist in isolated small arteries from men with established coronary heart disease (CHD) and with a history of myocardial infarction versus healthy male control subjects. As to methodology, small arteries obtained from subcutaneous fat biopsies and mounted on a wire myograph were preconstricted with norepinephrine, and dilator responses to increasing nanomolar-micromolar concentrations of the phytoestrogens resveratrol and genistein (predominantly ERbeta agonists) and to propyl-[1H]-pyrazole-1,3,5-triyl-trisplenol (PPT, a selective ERalpha agonist) were determined. These were compared with responses to reference compound 17beta-estradiol (17beta-E2). Concentration-response curves were constructed before and after nitric oxide (NO) synthase inhibition with Nomega-nitro-L-arginine methyl ester. As a result, relaxation induced by the investigated compounds was similar in men with CHD and control men, but in both groups PPT and genistein-induced relaxation was greater than that of resveratrol and 17beta-E2. NO contributed to both phytoestrogens and PPT-induced relaxation but not to 17beta-E2 responses in arteries from control men. This NO-mediated component of relaxation was absent in arteries from men with established CHD. In conclusion, phytoestrogens, at concentrations achievable by ingestion of phytoestrogen-rich food products, evoke dilatation ex vivo of small peripheral arteries from normal men and those with established CHD. The contribution of NO to dilatory responses by these compounds is pertinent to arteries from control males, whereas other NO-independent dilatory mechanism(s) are involved in arteries from CHD.

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“…Three subtypes of the ER have been identified: ER-␣, ER-␤, and GPR30 (3,7,29,39,43). Some studies have shown that the ERs have different patterns of expression and different effects at different ages (12,14).…”

Section: Discussionmentioning

confidence: 99%

Age and sex differences in vascular responsiveness in healthy and trauma patients: contribution of estrogen receptor-mediated Rho kinase and PKC pathways

Xiao

Zhang

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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L. Age and sex differences in vascular responsiveness in healthy and trauma patients: contribution of estrogen receptor-mediated Rho kinase and PKC pathways. Am J Physiol Heart Circ Physiol 306: H1105-H1115, 2014. First published February 15, 2014 doi:10.1152/ajpheart.00645.2013.-Several medical conditions exhibit age-and sex-based differences. Whether or not traumatic shock exhibits such differences with regard to vascular responsiveness is not clear. In a cohort of 177 healthy subjects and 842 trauma patients (21-82 years) as well as different ages (4,8,10,14,18, and 24 wk; 1 and 1.5 years) and sexes of Sprague-Dawley normal and traumatic shock rats, the age-and sex-based differences of vascular responsiveness and the underlying mechanisms were investigated. Middle-aged and young women as well as female rats of reproductive age had higher vascular responsiveness in the normal condition and a lower decrease in vascular responsiveness after traumatic shock than older men and male rats of identical age. Exogenous supplementation of 17␤-estrdiol increased vascular reactivity in both male and femal rats of 8 -24 wk and preserved vascular responsiveness in rats following traumatic shock. No effect was observed in rats 1 to 1.5 years. These protective effects of estrogen were closely related to G protein-coupled receptor (GPR)30, estrogen receptor-mediated Rho kinase, and PKC pathway activation. Vascular responsiveness exhibits age-and sex-based differences in healthy subjects and trauma patients. Estrogen and its receptor (GPR30) mediated activation of Rho kinase and PKC using genomic and nongenomic mechanisms to elicit protective effects in vascular responsiveness. This finding is important for the personalized treatment for several age-and sex-related diseases involving estrogen. vascular reactivity; sex; age; estrogen; estrogen receptor; Rho kinase; PKC IN RECENT YEARS, INTEREST in studying the effects of sex hormones and gender on cardiovascular function has been growing. Basic and clinical investigations have shown important differences in the structure and function of the cardiovascular system between men and women (32). Several studies have shown that premenopausal women are protected from most cardiovascular events as compared with men (26). However, after the menopause, women are at an increased risk of cardiovascular complications as compared with premenopausal women (26). The pathophysiological mechanisms for such differences are not clear, but studies have shown that sex steroids make some contribution (30,36,42).Trauma is often seen in civilian and military situations. Hemorrhage and hemorrhagic shock are the major causes of early deaths in injured soldiers and in injuries due to accidents. Studies have shown that traumatic hemorrhagic shock accounts for Ϸ50% of deaths of battle personnel and for 66%-80% of trauma deaths (8, 13). Vascular responsiveness is a key factor in maintaining vascular tone and hemodynamic stability, helps to determine tissue perfusion, and affects other organ functions (23,24). ...

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Dilatory responses to estrogenic compounds in small femoral arteries of male and female estrogen receptor-β knockout mice

Cited by 21 publications

References 60 publications

Selective estrogen receptor-α and estrogen receptor-β agonists rapidly decrease pulmonary artery vasoconstriction by a nitric oxide-dependent mechanism

Selective estrogen receptor-α and estrogen receptor-β agonists rapidly decrease pulmonary artery vasoconstriction by a nitric oxide-dependent mechanism

Acute responses to phytoestrogens in small arteries from men with coronary heart disease

Age and sex differences in vascular responsiveness in healthy and trauma patients: contribution of estrogen receptor-mediated Rho kinase and PKC pathways

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