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

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

doi:10.1152/ajpregu.00626.2009

Cited by 58 publications

(55 citation statements)

References 44 publications

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“…Secondly, our study population was not gender equivalent, with only 14 of the 40 subjects (7 in each experimental group) being women. Although we observed no effect of gender in the present study, gender-differences in ET-1 system activity have been reported (27). Given the relatively modest number of women in our study, we are unable to be conclusive regarding possible gender interactions/differences with MetS-related influences on ET-1 vasoconstriction tone.…”

Section: Discussioncontrasting

confidence: 87%

Metabolic syndrome and endothelin-1 mediated vasoconstrictor tone in overweight/obese adults

et al. 2014

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Objective To determine whether endothelin (ET)-1 vasoconstrictor tone is greater in overweight and obese adults with the metabolic syndrome (MetS). Materials/Methods Forty overweight/obese middle-aged and older adults (age: 43-71 years; BMI: 25.1-36.9 kg/m2) were studied: 20 without MetS (13 M/7 F) and 20 with MetS (13 M/7 F). MetS was established according to NCEP ATP III guidelines. Forearm blood flow (FBF; plethysmography) responses to intra-arterial infusion of selective ETA receptor blockade (BQ-123; 100 nmol/min; for 60 min) and non-selective ETA/B receptor blockade (BQ-123 + BQ-788 [50 nmol/min for 60 min]) were determined. Results In response to the selective ETA antagonism, there was a significant increase in forearm blood flow from baseline in both groups. However, the increase in forearm blood flow was significantly higher (P=0.03; ~45%) in the overweight/obese group with MetS than the group without MetS. In contrast, there were no significant group differences in FBF responses to non-selective ETA/B receptor blockade. Peak vasodilator responses to nonselective ETA/B blockade were ~50% higher than baseline blood flow in the overweight/obese groups without and with MetS. Conclusion MetS is associated with higher ET-1 vasoconstrictor tone in overweight/obese adults. The enhanced ET-1 vasoconstrictor activity with MetS is mediated by the ETA receptor subtype.

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Section: Discussioncontrasting

confidence: 87%

Metabolic syndrome and endothelin-1 mediated vasoconstrictor tone in overweight/obese adults

et al. 2014

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“…Indeed, although a fall in BP for cardiac cycles without an MSNA burst was seen in all groups, it was ϳ132% greater in older men. Thus, despite the fact that aging is associated with increased synthesis and action of vasoconstrictors (4,40,45), such as endothelin, and angiotensin II, our results highlight the importance and necessity of higher sympathetic outflow to the skeletal muscle vasculature in older men to regulate and maintain beat-to-beat BP. Of note, the larger falls in BP may be expected to contribute to greater BP variability in older men (39), which has been suggested to be associated with end organ damage (27,(32)(33)(34).…”

Section: Discussionmentioning

confidence: 61%

Influence of age and sex on the pressor response following a spontaneous burst of muscle sympathetic nerve activity

Vianna

Hart

Fairfax

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

100

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The sympathetic nervous system is critical for the beat-to-beat regulation of arterial blood pressure (BP). Although studies have examined age- and sex-related effects on BP control, findings are inconsistent and limited data are available in postmenopausal women. In addition, the majority of studies have focused on time-averaged responses without consideration for potential beat-to-beat alterations. Thus we examined whether the ability of muscle sympathetic nerve activity (MSNA) to modulate BP on a beat-to-beat basis is affected by age or sex. BP and MSNA were measured during supine rest in 40 young (20 men) and 40 older (20 men) healthy subjects. Beat-to-beat fluctuations in mean arterial pressure (MAP) were characterized for 15 cardiac cycles after each MSNA burst using signal averaging. The rise in MAP following an MSNA burst was similar between young men and women (+2.64 ± 0.3 vs. +2.57 ± 0.3 mmHg, respectively). However, the magnitude of the increase in MAP after an MSNA burst was reduced in older compared with young subjects (P < 0.05). Moreover, the attenuation of the pressor response was greater in older women (+1.20 ± 0.1 mmHg) compared with older men (+1.72 ± 0.2 mmHg; P < 0.05). Interestingly, in all groups, MAP consistently decreased after cardiac cycles without MSNA bursts (nonbursts) with the magnitude of fall greatest in older men. In summary, healthy aging is associated with an attenuated beat-to-beat increase in BP after a spontaneous MSNA burst, and this attenuation is more pronounced in postmenopausal women. Furthermore, our nonburst findings highlight the importance of sympathetic vasoconstrictor activity to maintain beat-to-beat BP, particularly in older men.

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“…Vasomotor tone has been shown to be lower in coronary arteries in females than in males, which may in part be due to sex hormone effects 24,25 , although other mechanisms have also been implicated including gender-related differences in autonomic regulation 26,27 and in responses to oxidative stress 28 , adenosine 29 , endothelin-1 30 , angiotensin II 31 , among other stimuli. 32 Risk factors such as diabetes, hypertension and dyslipidemia were highly prevalent among both genders in our study sample.…”

Section: Discussionmentioning

confidence: 99%

Effects of Sex on Coronary Microvascular Dysfunction and Cardiac Outcomes

Naya²,

et al. 2014

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Background Coronary microvascular dysfunction (CMD) is a prevalent and prognostically important finding in patients with symptoms suggestive of coronary artery disease (CAD). The relative extent to which CMD affects both genders is largely unknown. Methods and Results We investigated 405 men and 813 women referred for evaluation of suspected CAD with no previous history of CAD and no visual evidence of CAD on rest/stress positron emission tomography (PET) myocardial perfusion imaging. Coronary flow reserve (CFR) was quantified and CFR<2.0 used to define the presence of CMD. Major adverse cardiac events (MACE), including cardiac death, non-fatal myocardial infarction, late revascularization and hospitalization for heart failure, were assessed in blinded fashion over a median follow-up of 1.3 years (IQR 0.5–2.3 years). CMD was highly prevalent both in men and women (51% and 54%, respectively; P(Fisher exact test)=0.39; P(equivalence)=0.0002). Regardless of gender, CFR was a powerful incremental predictor of MACE (hazard ratio 0.80 [95% CI 0.75–086] per 10% increase in CFR; P<0.0001) and resulted in favorable net reclassification improvement (NRI=0.280 [95% CI 0.049–0.512]), after adjustment for clinical risk and ventricular function. In a subgroup (N=404; 307 female/97 male) without evidence of coronary artery calcification (CAC) on gated CT imaging, CMD was common in both genders, despite normal stress perfusion imaging and zero CAC (44% of men versus 48% of women; P(Fisher exact test)=0.56; P(equivalence)=0.041). Conclusions CMD is highly prevalent among at risk individuals and is associated with adverse outcomes regardless of gender. The high prevalence of CMD in both genders suggests that it may be a useful target for future therapeutic interventions.

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

Cited by 58 publications

References 44 publications

Metabolic syndrome and endothelin-1 mediated vasoconstrictor tone in overweight/obese adults

Metabolic syndrome and endothelin-1 mediated vasoconstrictor tone in overweight/obese adults

Influence of age and sex on the pressor response following a spontaneous burst of muscle sympathetic nerve activity

Effects of Sex on Coronary Microvascular Dysfunction and Cardiac Outcomes

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