Male–female differences in the relative contribution of endothelial vasodilators released by rat tail artery

Pak, Kirk J.; Geary, Greg G.; Duckles, Sue Piper; Krause, Diana N.

doi:10.1016/s0024-3205(02)01851-9

Cited by 31 publications

(28 citation statements)

References 30 publications

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“…crucial in this modulation, especially given the fact that in the resistance vasculature the predominant mediators implicated in endothelium-dependent relaxation in males are NO and PGI 2 , whereas in females it is EDHF (McCulloch & Randall 1998, Pak et al 2002, Scotland et al 2005b.…”

Section: Edhfmentioning

confidence: 99%

“…Since EDHF plays a more prominent role in endothelium-dependent relaxation of resistance versus conduit arteries (Shimokawa et al 1996), data from the EDHF mouse suggests that sex hormones regulate EDHF activity and that this may play a critical role in the maintenance of physiological levels of blood pressure and endothelial function in females (Scotland et al 2005b). Consequently, enhanced EDHF function in females compared with males (McCulloch & Randall 1998, Pak et al 2002, Scotland et al 2005b) might afford the cardioprotective phenotype of females.…”

Section: Edhfmentioning

confidence: 99%

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Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Villar¹,

Hobbs²,

Ahluwalia

2008

Journal of Endocrinology

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The vascular endothelium plays a crucial role in the regulation of vascular homeostasis by controlling vascular tone, coagulation, and inflammatory responses. These actions are exerted by endothelial factors including nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). The greater incidence of cardiovascular disease (CVD) in men and postmenopausal women compared with premenopausal women implies a vasoprotective phenotype of females, which may be influenced by sex hormones. These hormones, particularly estrogen, have modulatory effects on the endothelium and circulating cells that have been implicated in vascular inflammation and in the development of CVD. EDHF seems to be the predominant endothelial factor in the resistance vasculature of females and this mediator could afford the beneficial cardiovascular risk profile observed in premenopausal woman. In this review, we discuss sex differences in EDHF biology and how sex hormones can modulate EDHF responses. We also review the implication of sex hormone-dependent regulation of EDHF in inflammatory processes, platelet function, and repair after vascular damage, each of which have a critical role in several aspects of the pathogenesis of CVD.

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Section: Edhfmentioning

confidence: 99%

Section: Edhfmentioning

confidence: 99%

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Villar¹,

Hobbs²,

Ahluwalia

2008

Journal of Endocrinology

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“…Prostaglandins (PGs) and endothelium-derived hyperpolarizing factor (EDHF) also contribute to endotheliumdependent relaxation in animal models, and there are sex differences in the magnitude of the dilatory response and pathways activated by increased shear stress (26,41,51). For example, shear stress-induced dilations in rat tail arteries are fully NO dependent in male rats but NO and EDHF dependent in female rats (41). In NO and PG knockout mice, females but not males maintain mesenteric artery endothelium-dependent dilation, suggesting a greater compensatory role of EDHF in female mice (51).…”

mentioning

confidence: 99%

Heterogenous vasodilator pathways underlie flow-mediated dilation in men and women

Parker

Tschakovsky

Augeri

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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FJ. Heterogenous vasodilator pathways underlie flowmediated dilation in men and women. Am J Physiol Heart Circ Physiol 301: H1118 -H1126, 2011. First published June 3, 2011 doi:10.1152/ajpheart.00400.2011.-This study investigated the sex differences in the contribution of nitric oxide (NO) and prostaglandins (PGs) to flow-mediated dilation (FMD). Radial artery (RA) FMD, assessed as the dilatory response to 5-min distal cuff occlusion, was repeated after three separate brachial artery infusions of saline (SAL),, and ketorolac (KETO) ϩ L-NMMA in healthy younger men (M; n ϭ 8) and women (W; n ϭ 8).In eight subjects (4 M, 4W) RA FMD was reassessed on a separate day with drug order reversed (SAL, KETO, and L-NMMA ϩ KETO). RA FMD was calculated as the peak dilatory response observed relative to baseline (%FMD) and expressed relative to the corresponding area under the curve shear stress (%FMD/AUC SS). L-NMMA reduced %FMD similarly and modestly (P ϭ 0.68 for sex * trial interaction) in M and W (all subjects: 10.0 Ϯ 3.8 to 7.6 Ϯ 4.7%; P ϭ 0.03) with no further effect of KETO (P ϭ 0.68). However, all sex * trial and trial effects on %FMD/AUC SS for L-NMMA and KETO ϩ L-NMMA were insignificant (all P Ͼ 0.20). There was also substantial heterogeneity of the magnitude and direction of dilator responses to blockade. After L-NMMA infusion, subjects exhibited both reduced (n ϭ 14; range: 11 to 78% decrease) and augmented (n ϭ 2; range: 1 to 96% increase) %FMD. Following KETO ϩ L-NMMA, seven subjects exhibited reduced dilation (range: 10 to 115% decrease) and nine subjects exhibited augmented dilation (range: 1 to 212% increase). Reversing drug order did not change the nature of the findings. These findings suggest that RA FMD is not fully or uniformly NO dependent in either men or women, and that there is heterogeneity in the pathways underlying the conduit dilatory response to ischemia. shear stress; nitric oxide; prostaglandins; vasodilation BRACHIAL ARTERY FLOW-MEDIATED dilation (FMD), the shearevoked conduit artery dilatory response to a period of tissue ischemia, is a standard noninvasive technique for assessing endothelial function and has been correlated with coronary artery endothelial function (3). FMD is predictive of future cardiovascular events (21, 60), providing independent prognostic value to cardiovascular risk assessment in post menopausal women (48) and predicting future cardiac events in patients with established coronary artery disease (7).Reductions in FMD are widely assumed to reflect diminished nitric oxide (NO) dilator function as several pivotal human studies have concluded that brachial and radial artery FMD are dependent on a NO pathway (12,28,29,40). In these studies, blockade of NO by administration of the endothelial nitric oxide synthase (eNOS) inhibitor [N G -monomethyl-Larginine (L-NMMA)] in young, healthy humans abolished the conduit dilatory response to a 5-min period of distal occlusion. By contrast, a recent study (44) was unable to reduce radial FMD with a large dose of L-NMMA and conclude...

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“…In clinical characteristics, the ratio of HT and current smoking of men was significantly higher than that of women (73 vs. 54.5%, P ϭ (12) reported that the spasm group has a high ratio of men, smokers, and HT. Spasm is defined by the presence of epicardial vasodilation; herein, the definition of CMVD was completely different, but it is reported that men have more influence of NO than women in vascular tone (17,24,33). Thus it is possible that the factors of decreasing NO as HT and smoking are predicted as incidence of CMVD, especially in men.…”

Section: Discussionmentioning

confidence: 99%

“…CMVD is more frequently found in women, because EET shows a greater effect than nitric oxide (NO) on vascular tone in microcirculation (17,24). Moreover, EET was more effective in female mice than in male mice (33).…”

Section: Discussionmentioning

confidence: 99%

Sex differences in the impact of CYP2C19 polymorphisms and low-grade inflammation on coronary microvascular disorder

Akasaka

Hokimoto

Sueta

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Categorization as a cytochrome P-450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. It is correlated with an increase in the circulating levels of high-sense C-reactive protein (hs-CRP) in women only, although its role in coronary microcirculation is unclear. We examined sex differences in the impact of the CYP2C19 genotype and low-grade inflammation on coronary microvascular disorder (CMVD). We examined CYP2C19 genotypes in patients with CMVD (n ϭ 81) and in healthy subjects as control (n ϭ 81). CMVD was defined as the absence of coronary artery stenosis and epicardial spasms, the presence of inverted lactic acid levels between the intracoronary and coronary sinuses, or an adenosine triphosphate-induced coronary flow reserve ratio Ͻ 2.5. CYP2C19 PMs have two loss-of-function (LOF) alleles (*2, *3). Extensive metabolizers have no LOF alleles, and intermediate metabolizers have one LOF allele. The ratio of CYP2C19 PM and hs-CRP levels in CMVD was significantly higher than that of controls, especially in women (40.9 vs. 13.8%, P ϭ 0.013; 0.11 Ϯ 0.06 vs. 0.07 Ϯ 0.04 mg/dl, P ϭ 0.001). Moreover, in each CYP2C19 genotype, hs-CRP levels in CMVD in CYP2C19 PMs were significantly higher than those of the controls, especially in women (0.15 Ϯ 0.06 vs. 0.07 Ϯ 0.03, P ϭ 0.004). Multivariate analysis for CMVD indicated that the female sex, current smoking, and hypertension were predictive factors, and that high levels of hs-CRP and CYP2C19 PM were predictive factors in women only (odds ratio 3.5, 95% confidence interval 1.26 -9.93, P ϭ 0.033; odds ratio 4.1, 95% confidence interval 1.15-14.1, P ϭ 0.038). CYP2C19 PM genotype may be a new candidate risk factor for CMVD via inflammation exclusively in the female population.

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Male–female differences in the relative contribution of endothelial vasodilators released by rat tail artery

Cited by 31 publications

References 30 publications

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Heterogenous vasodilator pathways underlie flow-mediated dilation in men and women

Sex differences in the impact of CYP2C19 polymorphisms and low-grade inflammation on coronary microvascular disorder

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