Oestrogen modulates vascular adrenergic reactivity of the spontaneously hypertensive rat

Brandin, Lisa; Bergström, Göran; Manhem, Karin; Gustafsson, Helena

doi:10.1097/00004872-200309000-00019

Cited by 19 publications

(21 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…27 Other studies reported that ovariectomy did not affect NE-induced arterial constriction. 28 Yet other studies reported that ovariectomy decreased arterial responses to NE 29 and that estrogen treatment enhanced NE-induced constriction in arteries. 30 Far fewer data address the effect of ovariectomy of ovarian steroids on venous responses to NE.…”

Section: Discussionmentioning

confidence: 97%

Effect of Ovariectomy on Blood Pressure and Venous Tone in Female Spontaneously Hypertensive Rats

Martin

Redetzke

Vogel

et al. 2008

American Journal of Hypertension

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 97%

Effect of Ovariectomy on Blood Pressure and Venous Tone in Female Spontaneously Hypertensive Rats

Martin

Redetzke

Vogel

et al. 2008

American Journal of Hypertension

View full text Add to dashboard Cite

show abstract

“…26 The gender specificity of the enhanced PE responsiveness observed in the ER␤KO mice shares similarities with small arteries from spontaneously hypertensive rats (SHR), in which enhanced adrenergic stimulation and increased blood pressure have been demonstrated in males 10 but not in females. 15,27 After OVX, adrenergic nerve stimulation also increases in small arteries from SHR females as a result of an ␣ 1 -AR-mediated response, whereas estrogen supplementation reversed this effect. 15 Despite enhanced constriction to PE, the similarity of responses to NE in ER␤KO and WT males suggested that ER-dependent modulation of ARs occurs to prevent enhanced NE constriction in ER␤KO males.…”

Section: Discussionmentioning

confidence: 99%

“…15,27 After OVX, adrenergic nerve stimulation also increases in small arteries from SHR females as a result of an ␣ 1 -AR-mediated response, whereas estrogen supplementation reversed this effect. 15 Despite enhanced constriction to PE, the similarity of responses to NE in ER␤KO and WT males suggested that ER-dependent modulation of ARs occurs to prevent enhanced NE constriction in ER␤KO males. Whereas PE constricts solely via ␣ 1 -AR on VSM cell, NE may modulate vasoconstriction via endothelial ␣ 2 -AR and release of endotheliumderived factors, 12,28,29 predominantly NO, 30 the contribution of which decreases with diminishing artery size.…”

Section: Discussionmentioning

confidence: 99%

Gender-Specific Alteration of Adrenergic Responses in Small Femoral Arteries From Estrogen Receptor-β Knockout Mice

et al. 2005

View full text Add to dashboard Cite

Abstract-Estrogen receptor-␤ knockout mice become hypertensive as they age, and males have a higher blood pressure than females. We hypothesized that the absence of estrogen receptor-␤ may contribute to development of cardiovascular dysfunction by modification of adrenergic responsiveness in the peripheral vasculature. Small femoral arteries (internal diameter Ͻ200 m) were isolated from estrogen receptor-␤ knockout and wild-type mice and mounted on a wire myograph. Concentration-response curves to phenylephrine and norepinephrine were compared and the contribution of adrenoceptor subtypes established using specific agonists and antagonists. The involvement of endothelial factors in the modulation of resting tone was also investigated and immunohistochemical analysis used to confirm the presence or absence of estrogen receptor expression. Compared with wild type, arteries from estrogen receptor-␤ knockout male, but not female, mice demonstrated gender-specific enhancement of the response to phenylephrine (␣ 1 -adrenoceptor agonist), which was accompanied by elevated basal tension attributable to endothelial factors. Contractile responses to the mixed adrenoceptor agonist norepinephrine did not differ significantly between estrogen receptor-␤ knockout and wild type; however, ␤-adrenoceptor inhibition unmasked an enhanced underlying ␣ 1 -adrenoceptor responsiveness in estrogen receptor-␤ knockout males. ␤-adrenoceptor-mediated dilatation was also enhanced in estrogen receptor-␤ knockout versus wild-type males. We suggest that estrogen receptor-␤ modifies the adrenergic control of small artery tone in males but not in females. Key Words: gender Ⅲ endothelium Ⅲ estrogen Ⅲ arteries Ⅲ vasoconstriction Ⅲ adrenergic receptor agonists E ndogenous estrogens are considered to play an important role in cardiovascular homeostasis. Through occupancy of estrogen receptors (ERs) ␣ (ER␣) and ␤ (ER␤), estrogens target genes that contribute to the regulation of vascular tone, the lipid profile, redox status, and vascular structure. However, the relative role of each ER subtype in cardiovascular responses to estrogens remains poorly understood. 1 ER␣ and ER␤ are expressed in the endothelium and in vascular smooth muscle (VSM), but expression of the ER subtypes is gender and vascular bed dependent. 2,3 The explicit role of ER subtypes in the cardiovascular system, particularly in relation to regulation of vascular tone, has been difficult to assess because of the lack of specific ER subtype antagonists or agonists. The development of genetically modified animals in which one or other of the ERs is disrupted provides a useful alternative strategy for investigation. Zhu et al 4 reported that absence of ER␤ leads to age-dependent hypertension in both genders of mice, and that blood pressure in males was higher. However, no mechanisms that could explain gender-related differences in hypertension were proposed, 4 and it is unlikely that the altered contractile function observed in the aorta of the ER␤ knockout (ER␤KO) mice 4 would predisp...

show abstract

“…Fresh bovine hearts were obtained from a local abattoir. Small coronary arteries (ϳ200 m inner diameter) were dissected and stored in cell culture medium, which were then mounted in a Multi Myograph 610M (Danish Myo Technology, Aarhus, Denmark) for recording of their isometric wall tension, as described previously (4,5). After 30 min of equilibration in physiological saline solution (pH 7.4) containing (in mM) 119 NaCl, 4.7 KCl, 1.6 CaCl 2, 1.17 MgSO4, 1.18 NaH2PO4, 2.24 NaHCO3, 0.026 EDTA, and 5.5 glucose, at 37°C, bubbled with a gas mixture of 95% O2 and 5% CO2, basic tension was set.…”

Section: Lc-esi-ms-ms Analysis Of Ceramidementioning

confidence: 99%

Triggering role of acid sphingomyelinase in endothelial lysosome-membrane fusion and dysfunction in coronary arteries

Bao

Xia

Poklis

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

The present study determined whether activation of acid sphingomyelinase (ASM) drives membrane proximal lysosomes to fuse to the cell surface, facilitating membrane lipid rafts (LRs) clustering in coronary arterial endothelial cells (CAECs) and leading to endothelial dysfunction. By confocal microscopy, the activators of ASM, phosphatidylinositol (PI), and bis (monoacylglyceryl) phosphate (Bis), and an inducer of ASM, butyrate, were found to increase LRs clustering in bovine CAECs, which was blocked by lysosome fusion inhibitor vacuolin-1. However, arsenic trioxide (Ars), an inducer of de novo synthesis of ceramide, had no such effect. Similarly, vacuolin-1-blockable effects were observed using fluorescence resonance energy transfer detection. Liquid chromatography-electrospray ionization-tandem mass spectrometry analysis demonstrated that all of these treatments, even Ars, increased ceramide production in CAECs. When ASM gene was silenced, all treatments except Ars no longer increased ceramide levels. Furthermore, dynamic fluorescence monitoring in live cells showed that PI and Bis stimulated lysosome-membrane fusion in CAECs. Functionally, PI and Bis impaired endothelium-dependent vasodilation in perfused coronary arteries, which was blocked by vacuolin-1 and a lysosome function inhibitor, bafilomycine. FasL (Fas ligand), a previously confirmed lysosome fusion stimulator as a comparison, also produced a similar effect. It is concluded that ASM activation serves as a triggering mechanism and driving force, leading to fusion of membrane proximal lysosomes into LR clusters on the cell membrane of CAECs, which represents a novel mechanism mediating endothelial dysfunction during death receptor activation or other pathological situation.

show abstract

Oestrogen modulates vascular adrenergic reactivity of the spontaneously hypertensive rat

Abstract: Increased adrenergic reactivity is not present in small arteries from female SHRs. The findings of this study suggest that oestrogen acts on prejunctional mechanisms, reducing full expression of hypertension and peripheral vascular pathology.

Cited by 19 publications

References 19 publications

Effect of Ovariectomy on Blood Pressure and Venous Tone in Female Spontaneously Hypertensive Rats

Effect of Ovariectomy on Blood Pressure and Venous Tone in Female Spontaneously Hypertensive Rats

Gender-Specific Alteration of Adrenergic Responses in Small Femoral Arteries From Estrogen Receptor-β Knockout Mice

Triggering role of acid sphingomyelinase in endothelial lysosome-membrane fusion and dysfunction in coronary arteries

Contact Info

Product

Resources

About