Endothelin-1 Vasoconstrictor Tone Increases With Age in Healthy Men But Can Be Reduced by Regular Aerobic Exercise

Guilder, Gary P. Van; Westby, Christian M.; Greiner, Jared J.; Stauffer, Brian L.; DeSouza, Christopher A.

doi:10.1161/hypertensionaha.107.088294

Cited by 144 publications

(158 citation statements)

References 59 publications

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“…Body mass index (BMI) was calculated as weight (kg) divided by height (m) squared. Minimal waist circumference was measured as previously described (41). Fasting plasma glucose, insulin, lipid, and lipoprotein concentrations were determined with standard techniques.…”

Section: Methodsmentioning

confidence: 99%

“…The mechanism behind this sex difference in CVD remains unidentified. We have previously demonstrated that ET-1-mediated vasoconstrictor tone increases with age in men, suggesting that ET-1 production and vasoconstrictor tone may contribute to the increased coronary heart disease risk in middle-aged men (41). Currently, it is unknown whether a sex difference in ET-1-mediated vasoconstrictor tone exists.…”

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confidence: 99%

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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: Methodsmentioning

confidence: 99%

mentioning

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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“…In contrast, vasoconstrictor pathways are upregulated in subjects with cardiovascular disease or risk, and aerobic training is able to partly reverse the contribution of ET-1 to baseline vascular tone in older humans (297,310). Exercise training is also associated with decreased plasma and muscle levels of ET-1 (191,227).…”

Section: Resistance Arteriesmentioning

confidence: 99%

Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli

Green

Hopman

Padilla

et al. 2017

Physiological Reviews

535

570

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On the 400 th anniversary of Harvey's Lumleian lectures, this review focusses on the impact of physical exercise on "hemodynamic" forces associated with the movement of blood through arteries in humans and the functional and structural adaptations that result from repeated episodic exposure to such stimuli. The late 20 th century discovery that endothelial cells modify arterial tone via paracrine transduction, provoked studies exploring the direct mechanical effects of blood flow and pressure on vascular function and adaptation in vivo. In this review, we address the impact of distinct hemodynamic signals that occur in response to exercise, the inter-relationships between these signals, the nature of the adaptive responses that manifest under different physiological conditions and the implications for human health.Exercise modifies blood flow, luminal shear stress, arterial pressure and tangential wall stress, all of which can transduce changes in arterial function, diameter and wall thickness.There are important clinical implications of the adaptation that occurs as a consequence of repeated hemodynamic stimulation associated with exercise training in humans, including impacts on atherosclerotic risk in conduit arteries, the control of blood pressure in resistance vessels, oxygen delivery and diffusion, and microvascular health. Exercise training studies have demonstrated that direct hemodynamic impacts on the health of the artery wall contribute substantially to the well-established decrease in cardiovascular risk attributed to physical activity.

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“…Aging is associated with higher endogenous ET-1 levels (mRNA and protein) in both plasma and vascular tissue in males and females (10,36,53,57) together with an altered ET A to ET B ratio (48). Functionally, an increase in ET-1-dependent vascular tone has been demonstrated in clinically healthy older men (99). Another recent study in healthy volunteers reported impaired endothelium-dependent dilation in older compared with young men, which was inversely correlated with ET-1 protein expression in the brachial artery endothelial cells (25).…”

Section: Endothelin System In Agingmentioning

confidence: 99%

Endothelin in the female vasculature: a role in aging?

Lekontseva

Chakrabarti

Davidge

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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vascular diseases are the leading cause of morbidity and mortality in the world. Aging is associated with an increased incidence of cardiovascular disease. Premenopausal women are relatively protected from vascular alterations compared with age-matched men, likely due to higher levels of the female sex hormones. However, these vasoprotective effects in women are attenuated after menopause. Thus, the vascular system in aging women is affected by both the aging process as well as loss of hormonal protection, positioning women of this age group at a high risk for cardiovascular diseases such as hypertension, myocardial infarction, and stroke. The endothelin system in general and endothelin-1 (ET-1) in particular plays an important role in the pathogenesis of vascular dysfunction associated with aging. Evidence suggests that the female sex steroids can interfere with the vascular expression and actions of ET-1 via several mechanisms, which may further contribute to pathological processes in the vasculature of aging women. In this review, we have summarized hormone-dependent vascular pathways whereby ET-1 may mediate the deleterious effects of aging in postmenopausal females.ET-1; menopause; estrogen; vasoconstriction; inflammation AGING OF THE VASCULAR SYSTEM is a complex process characterized by sustained proinflammatory and proconstrictor changes in the vascular microenvironment. The resulting structural and functional alterations in systemic vasculature lead to increased risk of cardiovascular diseases such as hypertension, myocardial infarction, and stroke in the aging population (12,18,51,70). In the absence of chronic preexisting conditions, such as diabetes, premenopausal women express a favorable cardiovascular phenotype compared with age-matched men, largely due to the vasoprotective role of ovarian steroids such as estrogen (92). An alteration in circulating sex hormones at menopause, such as the decrease in estrogens and a relative excess of androgens, is associated with the conversion from a low-to high-risk cardiovascular profile (19,56). Although the mechanisms underlying the pathogenesis of vascular dysfunction in postmenopausal women are not completely understood, it is believed to result from a complex interplay between the aging process and the decline in ovarian hormones like estrogen.Endothelin has emerged as one of the key mediators of vascular dysfunction and remodeling in aging. Interestingly, there is evidence that female sex steroids (in particular, estrogen) can regulate the endothelin system at various levels from gene transcription and posttranslational modification of the peptide to expression of its vascular receptors and postreceptor signaling events. This review will summarize current knowledge on the impact of aging and female sex hormones on the endothelin system, as well as outline directions where further research is needed. A better understanding of the role of endothelin in the pathogenesis of vascular dysfunction in postmenopausal women may lead to the development of novel sex-...

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Endothelin-1 Vasoconstrictor Tone Increases With Age in Healthy Men But Can Be Reduced by Regular Aerobic Exercise

Cited by 144 publications

References 59 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

Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli

Endothelin in the female vasculature: a role in aging?

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