Androgen regulation of rat renal angiotensinogen messenger RNA expression.

Ellison, Kristin E.; Ingelfinger, Julie R.; Pivor, Mitchell; Dzau, Victor J.

doi:10.1172/jci114102

Cited by 187 publications

(128 citation statements)

References 22 publications

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“…Studies by 2 independent laboratories have shown that androgens increase and castration decreases renal mRNA expression of angiotensinogen, the substrate for renin. 15,16 In our studies, PRA was found to be significantly reduced in castrated males when compared with either young males or old intact males. A reduction in PRA and thus angiotensin II is one mechanism by which glomerular capillary pressure could be reduced and renal function and morphology protected.…”

Section: Fortepiani Et Al Aging Androgens and Renal Injurysupporting

confidence: 49%

Role of Androgens in Mediating Renal Injury in Aging SHR

et al. 2003

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Abstract-Men have an increased risk of cardiovascular and renal diseases and develop greater renal injury despite similar levels of blood pressure when compared with women. The mechanisms responsible for this predisposition are unknown. Using the spontaneously hypertensive rat (SHR), we have found that androgens play an important role in the development of hypertension in young male SHR. However, the role that androgens play in age-related renal injury and dysfunction in SHR is unknown. Our hypothesis was that despite reductions in serum testosterone with age, androgens mediate renal injury and dysfunction in male SHR. Male SHR were castrated at 8 months of age, studied at 18 months of age, and compared with age-matched, intact males and young intact males (4 months). Serum testosterone was reduced by 30% in aging males compared with young SHR. With castration, blood pressure (mean arterial pressure [MAP]) was decreased by Ͼ20 mm Hg compared with old males, glomerular filtration rate (GFR) was increased by Ͼ35%, and renal vascular resistance (RVR) was reduced by Ͼ40%. MAP, GFR, and RVR in castrated, old males were similar to values in young males. With castration, glomerular sclerosis was reversed and proteinuria was also decreased by Ͼ80% when compared with old intact males. In addition, in castrated old males, plasma renin activity was decreased by 30% compared with old males and by 60% compared with young rats. The data support the hypothesis that despite a reduction in testosterone with age, androgens play an important role in age-related renal injury and dysfunction in SHR. Key Words: age Ⅲ aging Ⅲ androgens Ⅲ hypertension, renal Ⅲ renal disease C omparisons performed in age-matched groups show that men have higher blood pressures than women until old age, when blood pressures become similar. 1,2 Men also have a greater incidence of renal disease and proceed to end-stage renal failure faster than do women, even when exhibiting similar levels of blood pressure. 3 The kidneys of men also undergo greater decline in renal function with age than do the kidneys of women. 4,5 This suggests that male sex hormones might play a role in mediating cardiovascular disease in men. However, the role that androgens play in the control of blood pressure and renal injury in men, especially with age, is not clear.We have previously found that androgens play a role in the development of hypertension in young, spontaneously hypertensive rats (SHR), because castration at 5 to 7 weeks of age reduces blood pressure when measured at 4 months of age, and testosterone treatment of ovariectomized females increases blood pressure. 6,7 This difference in blood pressure between intact and castrated males is still present at 8 months of age, the oldest age we have studied thus far. 8 We also found that the renin-angiotensin system (RAS) plays an important role in the development of hypertension in young SHR, because blockade of the RAS with converting-enzyme inhibitors removed the sex difference in blood pressure, and testosterone treatmen...

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Section: Fortepiani Et Al Aging Androgens and Renal Injurysupporting

confidence: 49%

Role of Androgens in Mediating Renal Injury in Aging SHR

et al. 2003

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“…In female rats, testosterone treatment increases renin activity and angiotensinogen expression. 90,91 Moreover, high testosterone levels have been associated with increased vasoconstriction in sucrose-fed female rats 92 and increased levels of endothelin, a potent vasoconstrictor, in postmenopausal women. 15 Glucose and insulin metabolism Table 2 summarizes the cross-sectional and longitudinal studies that examined the association between testosterone, SHBG and markers of glucose and insulin metabolism.…”

Section: Cardiovascular Risk Factors and Diseasementioning

confidence: 99%

Testosterone, SHBG and cardiovascular health in postmenopausal women

Brand

Schouw

2010

Int J Impot Res

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Cardiovascular disease (CVD) affects men and women differently with women having a lower incidence and later onset of disease. Research has recently refocused interest on the cardiovascular role of androgens. The purpose of this review is to summarize the evidence available on the association between testosterone and cardiovascular health in postmenopausal women. Published studies relating testosterone and sex hormone-binding globulin (SHBG) to CVD and its risk factors were reviewed. Studies included in this review suggest that increased androgenicity, characterized by high testosterone and low SHBG levels, is associated with an adverse CVD risk factor profile in postmenopausal women. However, evidence for an association with cardiovascular events is lacking and it is uncertain whether the observed associations with endogenous testosterone have clinical implications regarding the use of postmenopausal testosterone therapy. Large-scale, longitudinal studies relating testosterone and SHBG levels to cardiovascular risk factors and endpoints are needed to determine the temporal relationship between androgenicity and cardiovascular risk and to ascertain the long-term efficacy and safety of testosterone therapy in postmenopausal women.

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“…Testosterone supplementation in rats stimulates production of angiotensinogen, the substrate for renin, in the kidney, activating the RAS. 34,35 Androgen supplementation in women is also associated with increased plasma endothelin. 36 In addition, supplementation of dihydrotestosterone (10 Ϫ9 M) in cultured mesangial cells from SHR causes an increase in oxidative stress and increases angiotensin type-1 (AT 1 ) receptor expression (Cucchiarelli and Reckelhoff, unpublished data, 2003).…”

Section: Possible Mechanisms Responsible For Postmenopausal Hypertensmentioning

confidence: 99%

Novel Mechanisms Responsible for Postmenopausal Hypertension

2004

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Abstract-Blood pressure increases in many women after menopause. Hypertension is one of the major risk factors for cardiovascular disease. However, the mechanisms responsible for the postmenopausal increase in blood pressure are yet to be elucidated. Various humoral systems have been proposed to play a role in postmenopausal hypertension, such as changes in estrogen/androgen ratios, increases in endothelin and oxidative stress, and activation of the renin-angiotensin system (RAS). In addition, obesity, type II diabetes, and activation of the sympathetic nervous system are common in postmenopausal women and may also play important roles. However, progress in elucidating the mechanisms responsible for postmenopausal hypertension has been hampered by the lack of a suitable animal model. The aging female spontaneously hypertensive rat (SHR) exhibits many of the characteristics found in postmenopausal women. In this review, some of the possible mechanisms that could play a role in postmenopausal hypertension are discussed, as well as the characteristics of the aged female SHR as a model to study. Key Words: endothelin Ⅲ renin-angiotensin system Ⅲ oxidative stress Ⅲ obesity Ⅲ diabetes mellitus Ⅲ sympathetic nervous system B efore menopause, blood pressure is typically lower in women than in age-matched men. 1 In aging men and women, systolic and diastolic blood pressures increase, although in later years the diastolic plateaus or even declines. [1][2][3] However, in postmenopausal women, the prevalence of hypertension and cardiovascular disease risk increases regardless of ethnic origin. Results from the National Health and Nutrition Examination Survey (NHANES III) showed that in Hispanic women and non-Hispanic black women, the prevalence of hypertension was similar to, or higher than, that in men by age 60 years. 4 In non-Hispanic white populations, the prevalence of hypertension was higher in women than in men by age 70 years. 4 The increase in blood pressure in postmenopausal women does not occur as soon as the ovary becomes senescent, but rather over a number of years. 5 The mechanisms responsible for the increased blood pressure in women after menopause are not known. This review focuses on the use of the spontaneously hypertensive rat as a model of postmenopausal hypertension and evaluates the possible mechanistic roles of the sex hormones, oxidative stress, endothelin, renin-angiotensin system (RAS), weight gain, and sympathetic activation in postmenopausal hypertension. Animal Model for the Study of Postmenopausal HypertensionThe elucidation of mechanisms responsible for postmenopausal hypertension has been stunted by lack of an animal model. Sheep, rabbits, nonhuman primates, rats, and mice have been used as models of various menopausal changes; 6 however, to our knowledge, there is no animal model of naturally occurring postmenopausal hypertension. There have been attempts to mimic menopause by ovariectomizing animals; 7,8 however, these have rarely taken into account the effect of aging and cessation of ova...

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Androgen regulation of rat renal angiotensinogen messenger RNA expression.

Cited by 187 publications

References 22 publications

Role of Androgens in Mediating Renal Injury in Aging SHR

Role of Androgens in Mediating Renal Injury in Aging SHR

Testosterone, SHBG and cardiovascular health in postmenopausal women

Novel Mechanisms Responsible for Postmenopausal Hypertension

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