Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats.

Chen, Yiu-Fai; Naftilan, Allen J.; Oparil, Suzanne

doi:10.1161/01.hyp.19.5.456

Cited by 225 publications

(163 citation statements)

References 43 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: 53%

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: 53%

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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“…For example, testosterone treatment in ovariectomized (OVX) female rats increases plasma renin activity, while plasma renin activity, plasma angiotensin-converting enzyme activity and angiotensinogen mRNA decrease after castration of males (24,25). In contrast, E2 may decrease components of the renin-angiotensin system (23).…”

Section: Sex Differences In Angiotensin Iiinduced Hypertensionmentioning

confidence: 99%

Sex differences in angiotensin II- induced hypertension

Xue¹,

Johnson²,

Hay³

2007

Braz J Med Biol Res

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Sex differences in the development of hypertension and cardiovascular disease have been described in humans and in animal models. In this paper we will review some of our studies which have as their emphasis the examination of the role of sex differences and sex steroids in modulating the central actions of angiotensin II (ANG II) via interactions with free radicals and nitric oxide, generating pathways within brain circumventricular organs and in central sympathomodulatory systems. Our studies indicate that low-dose infusions of ANG II result in hypertension in wild-type male mice but not in intact wild-type females. Furthermore, we have demonstrated that ANG IIinduced hypertension in males is blocked by central infusions of the androgen receptor antagonist, flutamide, and by central infusions of the superoxide dismutase mimetic, tempol. We have also found that, in comparison to females, males show greater levels of intracellular reactive oxygen species in circumventricular organ neurons following long-term ANG II infusions. In female mice, ovariectomy, central blockade of estrogen receptors or total knockout of estrogen α receptors augments the pressor effects of ANG II. Finally, in females but not in males, central blockade of nitric oxide synthase increases the pressor effects of ANG II. Taken together, these results suggest that sex differences and estrogen and testosterone play important roles in the development of ANG II-induced hypertension.

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Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats.

Cited by 225 publications

References 43 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

Sex differences in angiotensin II- induced hypertension

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