Testosterone Exacerbates Hypertension and Reduces Pressure-Natriuresis in Male Spontaneously Hypertensive Rats

Reckelhoff, Jane F.; Zhang, Huimin; Granger, Joey P.

doi:10.1161/01.hyp.31.1.435

Cited by 291 publications

(302 citation statements)

References 17 publications

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“…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 treatment of ovariectomized females was not capable of increasing their blood pressure.…”

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confidence: 88%

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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confidence: 88%

Role of Androgens in Mediating Renal Injury in Aging SHR

et al. 2003

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“…9 As shown in Figure 1, in younger SHR (ages 4 and 8 months), females have lower blood pressure than males. 6,9,10 However, by age 16 to 18 months, the blood pressure has increased by 25 to 35 mm Hg, compared with young females, and 15 mm Hg when compared with 8-month-old females. In addition, the sex difference in blood pressure no longer exists because of the increase in blood pressure in old females, whereas blood pressure in male SHR remains fairly stable after age 8 months.…”

Section: Animal Model For the Study Of Postmenopausal Hypertensionmentioning

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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“…The prevalence of essential hypertension is higher in men than in age-matched premenopausal women. 1,2 In hypertensive rat models, such as spontaneously hypertensive rats (SHR) 3,4 and Dahl-salt hypertensive rats, 5,6 males have higher blood pressures than do females.…”

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Gender Differences in the Dietary Lard-Induced Increase in Blood Pressure in Rats

2002

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Abstract-We investigated the difference between male and female rats in the increase in blood pressure (BP) when they were fed a lard-enriched diet. We also investigated the effect of a gonadectomy, with or without testosterone treatment, on the dietary lard-induced increase in BP. Wistar-strain male or female rats were bilaterally castrated or ovariectomized. Some of them were implanted subcutaneously with silicon tubes containing crystalline testosterone. Each group was fed either chow alone or chow in which 50% of the energy content was from substituted lard. Systolic blood pressure (SBP) was determined weekly during each 7-or 11-week feeding period. A steady-state plasma glucose method was used to determine the insulin sensitivity. The dietary lard-induced increase in SBP was observed at 5 weeks after the start of the feeding in the sham-operated male rats. In the sham-operated female rats, SBP did not change from the basal values until 11 weeks into the experimental period. Castration eliminated the dietary lard-induced increase in SBP. Ovariectomy had no effect on SBP throughout the experimental period in both diet groups. In castrated males given testosterone, SBP increased in a dose-dependent manner. In ovariectomized females given testosterone, SBP increased significantly in the lard-enriched diet group. The dietary lard developed an insulin resistance in both the sham-operated and gonadectomized rats. However, SBP increased only in the sham-operated male rats. These results suggest that the dietary lard-induced increase in SBP depends on the presence of testosterone. Key Words: blood pressure Ⅲ rats Ⅲ insulin resistance Ⅲ diet Ⅲ hormones Ⅲ gender A sexually dimorphic pattern has been observed in relation to blood pressure. The prevalence of essential hypertension is higher in men than in age-matched premenopausal women. 1,2 In hypertensive rat models, such as spontaneously hypertensive rats (SHR) 3,4 and Dahl-salt hypertensive rats, 5,6 males have higher blood pressures than do females.Although the mechanisms of the gender difference in regulating blood pressure have not been completely elucidated, some studies have demonstrated that androgen has a potential role. 3,4,7 It was reported that an increase in blood pressure was attenuated by castration in the hypertensive rat model. 3,4,7 Furthermore, the relationship between androgen and pressure-natriuresis is suggested to play a part in the mechanism of these genetic forms of hypertension. However, whether or not male hormones may increase blood pressure remains uncertain in the other forms of hypertension.We recently verified that some fat-enriched diets led to the development of an increase in systolic blood pressure (SBP) in male rats compared with pair-fed control animals. 8 In the study, the chronic feeding of 8-week-old male rats with a lard-enriched diet increased SBP 5 weeks after the start of the feeding. And the chronic lard feeding induced hyperinsulinemia and led to the development of insulin resistance. An insulin sensitivity enhancer, trog...

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Testosterone Exacerbates Hypertension and Reduces Pressure-Natriuresis in Male Spontaneously Hypertensive Rats

Cited by 291 publications

References 17 publications

Role of Androgens in Mediating Renal Injury in Aging SHR

Role of Androgens in Mediating Renal Injury in Aging SHR

Novel Mechanisms Responsible for Postmenopausal Hypertension

Gender Differences in the Dietary Lard-Induced Increase in Blood Pressure in Rats

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