Sex-specific genetic determinants for arterial stiffness in Dahl salt-sensitive hypertensive rats

Decano, Julius L.; Pasion, Khristine A.; Black, Nicole; Giordano, N.; Herrera, Victoria L. M.; Ruiz-Opazo, Nelson

doi:10.1186/s12863-015-0324-7

Cited by 10 publications

(6 citation statements)

References 32 publications

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“…Limited preclinical studies have examined potential sex differences in the mechanisms of arterial stiffness due to hypertension. Sex‐specific quantitative trait loci affecting aortic stiffness in the Dahl salt‐sensitive hypertensive rat model have recently been identified (Decano et al, ). In male spontaneously hypertensive rats, arterial stiffness was decreased with arotinolol, a nonselective α/β‐adrenoceptor blocker (W. Zhou et al, ).…”

Section: Sex Differences In the Impact Of Cvd Risk Factors On Arteriamentioning

confidence: 99%

Sex differences in mechanisms of arterial stiffness

DuPont

Kenney

Patel

et al. 2019

British J Pharmacology

197

150

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Arterial stiffness progressively increases with aging and is an independent predictor of cardiovascular disease (CVD) risk. Evidence supports that there are sex differences in the time course of aging-related arterial stiffness and the associated CVD risk, which increases disproportionately in postmenopausal women. The association between arterial stiffness and mortality is almost twofold higher in women versus men. The differential clinical characteristics of the development of arterial stiffness between men and women indicate the involvement of sex-specific mechanisms. This review summarizes the current literature on sex differences in vascular stiffness induced by aging, obesity, hypertension, and sex-specific risk factors as well as the impact of hormonal status, diet, and exercise on vascular stiffness in males andfemales. An understanding of the mechanisms driving sex differences in vascular stiffness has the potential to identify novel sex-specific therapies to lessen CVD risk, the leading cause of death in males and females.Large conduit arteries are composed of three layers: (a) the outer tunica adventitia, (b) the middle tunica media, and (c) the inner tunica intima, each of which contributes to the overall stiffness of the vessel wall (Figure 1). The tunica adventitia consists primarily of fibroblasts,

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Section: Sex Differences In the Impact Of Cvd Risk Factors On Arteriamentioning

confidence: 99%

Sex differences in mechanisms of arterial stiffness

DuPont

Kenney

Patel

et al. 2019

British J Pharmacology

197

150

View full text Add to dashboard Cite

show abstract

“…The list of inbred mouse strains used in this study was mostly common (up to 93%) with previous strain-screening studies for cardiovascular phenotypes (9,20,81). Because there are numerous examples of sex by genotype interactions for several traits and differences in vascular function have been reported for vessel segments from male and female animals (12,24,81), female animals were not included in the present study to improve the consistency for each measurement within strains and to limit any confounding variables that would affect the identification of significant genome-wide associations. Mice were housed in the same room under standard conditions (nonbarrier), maintained on a 12 h light-dark cycle (7:00 AM-7:00 PM) in a controlled temperature (21.0 -22.0°C) and allowed food (Standardize Laboratory Rodent Diet) and water ad libitum.…”

Section: Animalsmentioning

confidence: 99%

Strain survey and genetic analysis of vasoreactivity in mouse aorta

Kim

Avila

Massett

2016

Physiological Genomics

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Understanding the genetic influence on vascular reactivity is important for identifying genes underlying impaired vascular function. The purpose of this study was to characterize the genetic contribution to intrinsic vascular function and to identify loci associated with phenotypic variation in vascular reactivity in mice. Concentration response curves to phenylephrine (PE), potassium chloride (KCl), acetylcholine (ACh), and sodium nitroprusside (SNP) were generated in aortic rings from male mice (12 wk old) from 27 inbred mouse strains. Significant strain-dependent differences were found for both maximal responses and sensitivity for each agent, except for SNP Max (%). Strain differences for maximal responses to ACh, PE, and KCl varied by two- to fivefold. On the basis of these large strain differences, we performed genome-wide association mapping (GWAS) to identify loci associated with variation in responses to these agents. GWAS for responses to ACh identified four significant and 19 suggestive loci. Several suggestive loci for responses to SNP, PE, and KCl (including one significant locus for KCl EC) were also identified. These results demonstrate that intrinsic endothelial function, and more generally vascular function, is genetically determined and associated with multiple genomic loci. Furthermore, these results are supported by the finding that several genes residing in significant and suggestive loci for responses to ACh were previously identified in rat and/or human quantitative trait loci/GWAS for cardiovascular disease. This study represents the first step toward the unbiased comprehensive discovery of genetic determinants that regulate intrinsic vascular function, particularly endothelial function.

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“…Besides, cardiac outcomes were similar comparing female Leptin and Control groups independent of the age. Literature also reports that sex differences may be related to sex chromosomes, products of genes located on the X and Y chromosomes, not only to gonadal hormones [63][64][65][66] .…”

Section: Discussionmentioning

confidence: 99%

Leptin administration during lactation leads to different nutritional, biometric, hemodynamic, and cardiac outcomes in prepubertal and adult female Wistar rats

Souza

Pedro

Rocha

et al. 2021

J Dev Orig Health Dis

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Literature reports that insults, such as hormonal disturbances, during critical periods of development may modulate organism physiology and metabolism favoring cardiovascular diseases (CVDs) later in life. Studies show that leptin administration during lactation leads to cardiovascular dysfunction in young and adult male Wistar rats. However, there are sex differences regarding CVD. Thus, the present work aimed to investigate neonatal leptin administration’s consequences on different outcomes in female rats at prepubertal and adult age. Newborn Wistar female rats were divided into two groups, Leptin and Control, receiving daily subcutaneous injections of this adipokine (8 μg/100 g) or saline for the first 10 of 21 d of lactation. Nutritional, biometric, hemodynamic, and echocardiographic parameters, as well as maximal effort ergometer performance, were determined at postnatal days (PND) 30 and 150. Leptin group presented lower food intake (p = 0.0003) and higher feed efficiency (p = 0.0058) between PND 21 and 30. Differences concerning echocardiographic parameters revealed higher left ventricle internal diameter (LVID) in systole (p = 0.0051), as well as lower left ventricle ejection fraction (LVEF) (p = 0.0111) and fractional shortening (FS) (p = 0.0405) for this group at PND 30. Older rats treated with leptin during lactation presented only higher LVID in systole (p = 0.0270). Systolic blood pressure and maximum effort ergometer test performance was similar between groups at both ages. These data suggest that nutritional, biometric, and cardiac outcomes due to neonatal leptin administration in female rats are age-dependent.

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Sex-specific genetic determinants for arterial stiffness in Dahl salt-sensitive hypertensive rats

Cited by 10 publications

References 32 publications

Sex differences in mechanisms of arterial stiffness

Sex differences in mechanisms of arterial stiffness

Strain survey and genetic analysis of vasoreactivity in mouse aorta

Leptin administration during lactation leads to different nutritional, biometric, hemodynamic, and cardiac outcomes in prepubertal and adult female Wistar rats

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