Relative androgenicity, blood pressure levels, and cardiovascular risk factors in young healthy women*

Mantzoros, C. S.; Georgiadis, E.; Young, Rosalie F.; C, Evagelopoulou; Khoury, Sleman; Katsilambros, Nicholas; Sowers, James R.

doi:10.1016/0895-7061(95)00051-p

Cited by 44 publications

(40 citation statements)

References 38 publications

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“…40 It has been suggested that the sex difference in SUA is related to the uricosuric effect of estrogen 41 and that sex hormones have a role in the relationship between SUA and hypertension. 42 In the present study, a possible explanation for the observed sex differences could be the greater adiposity in females than in males, which is consistent with our observation that adjustment for adiposity led to higher attenuation of the effect sizes of SUA on BP in the former than in the latter. Our findings are consistent with the frequently postulated claim that abdominal fat, which is particularly active metabolically, 43 might be a key factor in sex differences, as both WC and BMI are strongly correlated with abdominal fat.…”

Section: Discussionsupporting

confidence: 91%

Impact of different adiposity measures on the relation between serum uric acid and blood pressure in young adults

et al. 2011

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Serum uric acid (SUA) concentration is independently associated with blood pressure (BP) in adults. We examined this association in young adults at an age where anti-hypertension treatment, other potential confounding factors and co-morbidity are unlikely to occur. We assessed BP, anthropometric variables including weight, height, waist circumference (WC), body fat percent (using bioimpedance), lifestyle behaviors, SUA and blood lipids in 549 participants aged 19-20 years from a population-based cohort study (Seychelles Child Development Study). Mean (s.d.) SUA was higher in males than females, 0.33 (0.08) and 0.24 (0.07) mmol l À1 , respectively. Body mass index (BMI) was higher in females than males but BP was markedly higher in males than in females. SUA was associated with both systolic and diastolic BP. However, the magnitude of the linear regression coefficients relating BP and SUA decreased by up to 50% upon adjustment for BMI, WC or body fat percent. The association between SUA and BP was not altered upon further adjustment for alcohol intake, smoking, triglycerides or renal function. In fully adjusted models, SUA remained associated with BP (Po0.05) in females. In conclusion, adiposity substantially decreased the association between SUA and BP in young adults, and BP was independently associated with SUA in females. These findings suggest a role of adiposity in the link between hyperuricemia and hypertension.

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Section: Discussionsupporting

confidence: 91%

Impact of different adiposity measures on the relation between serum uric acid and blood pressure in young adults

et al. 2011

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“…Nonetheless, extensive genetic segregation and linkage analyses indicate multigenic factors as responsible for a significant component of human essential hypertension (13-15, 25, 33). Furthermore, gender differences in incidence and severity have also suggested the involvement of a sexdependent mechanism in the pathogenesis of human hypertension (1,10,14,25,27,34,35). We report here that treatment of rats with 5␣-dihydrotestosterone (DHT), a metabolic stable androgen, induces the expression of kidney CYP 4A8, increases the capacity of the renal microcirculation to synthesize prohypertensive 20-HETE (3,4,22,29), and causes systemic hypertension.…”

mentioning

confidence: 85%

Androgen-mediated induction of the kidney arachidonate hydroxylases is associated with the development of hypertension

Nakagawa¹,

Marji

Schwartzman

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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Hypertension is a leading cause of cardiovascular, cerebral, and renal disease morbidity and mortality, and epidemiological evidence suggests a role for sex-dependent mechanisms in the pathophysiology of hypertension. We show here that treatment of rats with 5␣-dihydrotestosterone increases the activity of the kidney arachidonate /-1 hydroxylase and the biosynthesis of 20-HETE (165 and 177% of control untreated male and female rats, respectively) and raises the systolic blood pressures of male and females rats by 46 and 57 mmHg, respectively. These androgen effects are associated with an upregulation in the kidney levels of CYP 4A8 mRNA and a decrease in CYP 4A1 transcripts. Dissected renal microvessels, the target tissue for most of the prohypertensive actions of 20-HETE, show an androgen-dependent upregulation of vascular CYP 4A8 mRNA and a fourfold increase in 20-HETE synthase activity. We propose that androgens regulate renal function and systemic blood pressure through a combination of transcriptional and hemodynamic mechanisms that are ultimately responsible for the regulation of renovascular tone and function. P-450 eicosanoids; androgens; CYP 4A8A NOW CONSIDERABLE BODY of evidence shows that microsomal P-450s (CYPs) participate in the in vivo metabolism of arachidonic acid (AA) and that products of this P-450-catalyzed pathway are in vitro modulators of renal ion transport and vascular reactivity and may be involved in the regulation of systemic blood pressure (3, 4,22,29). During catalytic turnover, the P-450 monooxygenase(s) metabolize AA via /-1 hydroxylation (AA /-1 hydroxylase) to 19-and 20-HETE and/or epoxidation (AA epoxygenase) to 5,8,11,or 14,5). Recombinant CYPs 4A1, 4A2, 4A8, and to a lesser extent 4A3, support the hydroxylation of AA to either 20-HETE or to mixtures of 16,19,31). All four CYP 4A isoforms are expressed in the male rat kidney (4,16,19,31), with CYPs 4A1 and 4A2/4A3 characterized as the predominant microsomal AA /-1 hydroxylases (16). The transcriptional regulation of rat CYPs P-450 4A1 and 4A2/4A3 by the peroxisomal proliferator activated receptor-␣ (45), as well as the sexually dimorphic, testosterone-sensitive expression of rat CYPs 4A2 and 4A8 and of murine Cyp 4a12, has been reported (18,20,40,42).Studies with the spontaneously hypertensive-Wistar Kyoto (SHR/WKY) rat model of spontaneous hypertension, an extensively characterized model of genetic hypertension (29), suggest a role for renal CYP 4As in the pathophysiology of the disease (3, 29). Thus based on 1) temporal associations between the increases in blood pressure, renal CYP 4A expression and 20-HETE formation (3, 29), 2) experimental manipulations of CYP 4A activity and/or expression (29,32,43), and 3)

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“…Testosterone may act as a direct vasorelaxant through influence on the vascular wall endocrine/ paracrine factors. 32,[36][37][38] It is also reported that the vasorelaxing effect of testosterone is endothelium independent, with the possible involvement of potassium channel modulation. 39,40 There is a pressing need for epidemiological studies in Africa, to determine the risk factors for the development of hypertension in specific living circumstances.…”

Section: Introductionmentioning

confidence: 99%

Prolactin, testosterone and cortisol as possible markers of changes in cardiovascular function associated with urbanization

et al. 2002

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People living in large informal settlements in South Africa showed a significant increase in cardio/cerebrovascular disease. This study was undertaken to compare the cardiovascular and endocrine parameters of urbanized and rural black female and males. The hormone levels such as prolactin, cortisol and testosterone may also change with urbanization and could make a contribution to the high rate of hypertension. For this study, 1202 black subjects were selected from 37 randomly selected rural and urbanized settlements. Resting blood pressure was recorded with a Finapres apparatus. Cardiac output, stroke volume, heart rate, total peripheral vascular resistance and compliance had been obtained with the Fast Modelflow software program. An acute laboratory stressor (hand dynamometer exercise) was applied to challenge the cardiovascular system and the measurements were repeated. Blood sampling was done and hormone levels were determined by biochemical analyses. For females, significant lower levels of cortisol were found in the urban strata in comparison with the rural strata. The testosterone levels were significantly lower and the prolactin levels significantly higher for females in the informal settlements compared with the rural strata. It is noticeable that most cardiovascular parameters showed the highest changes with the application of the stressor in the informal settlement strata and the lowest in people living on farms for both male and female. The prolactin levels in males are significantly higher in the informal settlement stratum. Subjects living in informal settlements showed a noticeable endocrine pattern of ongoing stress that can be associated with changes in the cardiovascular parameters with urbanization. This can partly explain the reported high rate of cardio/cerbrovascular disease in black South Africans living in informal settlements.

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Relative androgenicity, blood pressure levels, and cardiovascular risk factors in young healthy women*

Cited by 44 publications

References 38 publications

Impact of different adiposity measures on the relation between serum uric acid and blood pressure in young adults

Impact of different adiposity measures on the relation between serum uric acid and blood pressure in young adults

Androgen-mediated induction of the kidney arachidonate hydroxylases is associated with the development of hypertension

Prolactin, testosterone and cortisol as possible markers of changes in cardiovascular function associated with urbanization

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