Age-Related Reduction in Estrogen Receptor–Mediated Mechanisms of Vascular Relaxation in Female Spontaneously Hypertensive Rats

Wynne, Foster; Payne, Jerry A.; Cain, Ashley E.; Reckelhoff, Jane F.; Khalil, Raouf A.

doi:10.1161/01.hyp.0000111833.82664.0c

Cited by 68 publications

(57 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This contrasts previous studies which demonstrated physiological concentrations of 17β-estradiol reduced the constrictive response to ET-1 in market-age pigs (Sudhir et al, 1997;Teoh et al, 1999). However, Wynne et al (2004) similarly found that advanced age decreases the inhibitory effect of 17β-estradiol on calcium influx.…”

Section: Discussioncontrasting

confidence: 99%

The enhanced endothelin-1-induced contraction in cultured coronary arteries from mature female pigs is not antagonized by 17β-estradiol

Tummala

Hill

2007

Vascular Pharmacology

View full text Add to dashboard Cite

We have previously reported that organ cultured coronary arteries from market-age pigs (6-9 months of age) exhibit an enhanced contraction to the atherosclerotic-associated peptide, endothelin-1 (ET-1). The objective of this study was to investigate the interaction of 17β-estradiol with ET-1 in organ cultured coronary arteries from older female pigs (3-4 years old). A cumulative-concentration response relationship (1 × 10 −9 M to 3 × 10 −7 M) was generated to ET-1, and the isometric tension measured in fresh and organ cultured (4 days at 37°C) arterial rings that were each pre-incubated for 50 minutes in different concentrations (1 × 10 −9 M to 1 × 10 −5 M) of 17β-estradiol. Compared to freshly used arteries, culturing induced a 2-fold increase in tension development to ET-1 (3 × 10 −7 M). Although 17β-estradiol previously relaxed pre-constricted (with a 60 mM KCl solution) arteries, it did not affect the constrictive response to ET-1. Also, using an ET-1 ELISA we found that 17β-estradiol did not effect ET-1 production in intact arteries. Our results indicate that 17β-estradiol does not attenuate the production and constrictive properties of ET-1 in coronary arteries demonstrating a dedifferentiated cell phenotype.

show abstract

Section: Discussioncontrasting

confidence: 99%

The enhanced endothelin-1-induced contraction in cultured coronary arteries from mature female pigs is not antagonized by 17β-estradiol

Tummala

Hill

2007

Vascular Pharmacology

View full text Add to dashboard Cite

show abstract

“…24 An alternative ex- planation for the absence of estrogen-induced vasodilation in HCAs, at least in women, is the change in estrogen receptor cellular localization during perimenopause. 25 Furthermore, estrogen inactivates reactive oxygen species like the vasodilator H 2 O 2 26,27 and alters the AT 1 /AT 2 receptor ratio. 28,29 Both phenomena will directly affect Ang II-induced vasoconstriction.…”

Section: Discussionmentioning

confidence: 99%

Nongenomic Effects of Aldosterone in the Human Heart

et al. 2005

View full text Add to dashboard Cite

Abstract-Aldosterone exerts rapid "nongenomic" effects in various nonrenal tissues. Here, we investigated whether such effects occur in the human heart. Trabeculae and coronary arteries obtained from 57 heart valve donors (25 males; 32 females; 17 to 66 years of age) were mounted in organ baths. Aldosterone decreased contractility in atrial and ventricular trabeculae by maximally 34Ϯ3% and 15Ϯ4%, respectively, within 5 to 15 minutes after its application. The protein kinase C (PKC) inhibitor chelerythrine chloride, but not the mineralocorticoid receptor antagonists spironolactone and eplerenone, blocked this effect. Aldosterone also relaxed trabeculae that were prestimulated with angiotensin II (Ang II), and its negative inotropic effects were mimicked by hydrocortisone (at 10-fold lower potency) but not 17␤-estradiol. Aldosterone concentrations required to reduce inotropy were present in failing but not in normal human hearts. Previous exposure of coronary arteries to 1 mol/L aldosterone or 17␤-estradiol (but not hydrocortisone) doubled the maximum contractile response (E max ) to Ang II. ⌬E max correlated with extracellular signal-regulated kinase (ERK) 1/2 phosphorylation (PϽ0.01). Spironolactone and eplerenone did not block the potentiating effect of aldosterone. Studies in porcine renal arteries showed that potentiation also occurred at pmol/L aldosterone levels but not at 17␤-estradiol levels Ͻ1 mol/L. Aldosterone did not potentiate the ␣ 1 -adrenoceptor agonist phenylephrine. In conclusion, aldosterone induces a negative inotropic response in human trabeculae (thereby antagonizing the positive inotropic actions of Ang II) and potentiates the vasoconstrictor effect of Ang II in coronary arteries. These effects are specific and involve PKC and ERK 1/2, respectively. Furthermore, they occur in a nongenomic manner, and require pathological aldosterone concentrations.

show abstract

“…Others, conversely, have described significant effects of aging on vascular function in middle aged female rats with risk for cardiovascular disease (Fortepiani et al, 2003;Wynne et al, 2004). However, the fact that those animal models normally display increased risk for cardiovascular disease at early stage, when they are young adults, they may not represent a good model to determine aging-and menopause-associated vascular modifications in women.…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Gathering of aging and estrogen withdrawal in vascular dysfunction of senescent accelerated mice

Novella

Dantas

Segarra

et al. 2010

Experimental Gerontology

View full text Add to dashboard Cite

of aging and estrogen withdrawal in vascular dysfunction of senescent accelerated mice. Experimental Gerontology, Elsevier, 2010, 45 (11) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT

show abstract

Age-Related Reduction in Estrogen Receptor–Mediated Mechanisms of Vascular Relaxation in Female Spontaneously Hypertensive Rats

Cited by 68 publications

References 54 publications

The enhanced endothelin-1-induced contraction in cultured coronary arteries from mature female pigs is not antagonized by 17β-estradiol

The enhanced endothelin-1-induced contraction in cultured coronary arteries from mature female pigs is not antagonized by 17β-estradiol

Nongenomic Effects of Aldosterone in the Human Heart

Gathering of aging and estrogen withdrawal in vascular dysfunction of senescent accelerated mice

Contact Info

Product

Resources

About