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Vascular dysfunction precedes hypertension associated with a blood pressure locus on rat chromosome 12.

ABSTRACT: We previously isolated a 6.1-Mb region of SS/Mcwi (Dahl salt-sensitive) rat chromosome 12 (13.4-19.5 Mb) that significantly elevated blood pressure (BP) (?+34 mmHg, P < 0.001) compared with the SS-12(BN) consomic control. In the present study, we examined the role of vascular dysfunction and remodeling in hypertension risk associated with the 6.1-Mb (13.4-19.5 Mb) locus on rat chromosome 12 by reducing dietary salt, which lowered BP levels so that there were no substantial differences in BP between strains. Consequently, any observed differences in the vasculature were considered BP-independent. We also reduced the candidate region from 6.1 Mb with 133 genes to 2 Mb with 23 genes by congenic mapping. Both the 2 Mb and 6.1 Mb congenic intervals were associated with hypercontractility and decreased elasticity of resistance vasculature prior to elevations of BP, suggesting that the vascular remodeling and dysfunction likely contribute to the pathogenesis of hypertension in these congenic models. Of the 23 genes within the narrowed congenic interval, 12 were differentially expressed between the resistance vasculature of the 2 Mb congenic and SS-12(BN) consomic strains. Among these, Grifin was consistently upregulated 2.7 ± 0.6-fold (P < 0.05) and 2.0 ± 0.3-fold (P < 0.01), and Chst12 was consistently downregulated -2.8 ± 0.3-fold (P < 0.01) and -4.4 ± 0.4-fold (P < 0.00001) in the 2 Mb congenic compared with SS-12(BN) consomic under normotensive and hypertensive conditions, respectively. A syntenic region on human chromosome 7 has also been associated with BP regulation, suggesting that identification of the genetic mechanism(s) underlying cardiovascular phenotypes in this congenic strain will likely be translated to a better understanding of human hypertension.

SUBMITTER: Prisco SZ

PROVIDER: S-EPMC4200336 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Vascular dysfunction precedes hypertension associated with a blood pressure locus on rat chromosome 12.

Prisco Sasha Z SZ Priestley Jessica R C JR Weinberg Brian D BD Prisco Anthony R AR Hoffman Matthew J MJ Jacob Howard J HJ Flister Michael J MJ Lombard Julian H JH Lazar Jozef J

American journal of physiology. Heart and circulatory physiology 20140822 8

We previously isolated a 6.1-Mb region of SS/Mcwi (Dahl salt-sensitive) rat chromosome 12 (13.4-19.5 Mb) that significantly elevated blood pressure (BP) (Δ+34 mmHg, P < 0.001) compared with the SS-12(BN) consomic control. In the present study, we examined the role of vascular dysfunction and remodeling in hypertension risk associated with the 6.1-Mb (13.4-19.5 Mb) locus on rat chromosome 12 by reducing dietary salt, which lowered BP levels so that there were no substantial differences in BP betw ...[more]

PMID: 25320330

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Project description:INTRODUCTION:Sexual function, an important component of quality of life, is gaining increased research and clinical attention in older women with hypertension. AIM:To assess the association between systolic blood pressure (SBP) and other variables, and sexual activity and sexual dysfunction in hypertensive women. METHODS:Baseline analysis of 635 women participants of a larger randomized clinical trial of 9361 men and women. MAIN OUTCOME MEASURES:Self-reported sexual activity (yes/no), and sexual function using the Female Sexual Function Inventory (FSFI). RESULTS:452 participants (71.2%) reported having no sexual activity during the previous 4 weeks. The mean (SD) FSFI score for sexually active participants was 25.3 (6.0), and 52.6% of the sample reported a FSFI score ?26.55 designating sexual dysfunction. In logistic regression models, SBP was not significantly associated with sexual activity (AOR = 1.002; P > .05). Older age (AOR = 0.95, P < .05), and lower education (AOR for < high school vs college degree = 0.29, P < .05) were associated with lower odds of being sexually active, as was living alone versus living with others (AOR = 0.56, P < .05). Higher weekly alcohol consumption was associated with increased odds of being sexually active (AOR = 1.39; P < .05). In logistic regression models among sexually active participants, SBP was not associated with sexual dysfunction (AOR = 1.01; P > .05). Higher depressive symptoms from the Patient Health Questionnaire-9 (PHQ-9) was associated with higher odds of sexual dysfunction (AOR = 1.24, P < .05), as was increased number of physical comorbidities (AOR = 1.25, P < .05). Diuretic use was associated with lower odds of being sexually active in participants with chronic kidney disease (AOR = 0.33, P < .05). CONCLUSION:Younger age, higher education, living with others, and higher weekly alcohol consumption were significantly associated with higher odds of being sexually active in a sample of middle-aged and older women with hypertension. Increased depressive symptoms and increased physical comorbidities were significantly associated with increased odds of sexual dysfunction. SBP was not significantly associated with sexual activity or sexual dysfunction.

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Vascular dysfunction precedes hypertension associated with a blood pressure locus on rat chromosome 12.

Publications

Vascular dysfunction precedes hypertension associated with a blood pressure locus on rat chromosome 12.

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