Castration reduces blood pressure and autonomic venous tone in male spontaneously hypertensive rats

Martin, Doug; Biltoft, Scott; Redetzke, Rebecca A.; Vogel, Erin

doi:10.1097/01.hjh.0000191903.19230.79

Cited by 26 publications

(22 citation statements)

References 46 publications

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“…Androgen involvement related to hypertension is reported in human and animal studies in which increases in testosterone levels are associated with increases in blood pressure (11,18,20,23,34,41). Furthermore, several experimental models of hypertension show that castration reduces hypertension, an effect reversed by testosterone replacement (22).…”

Section: Discussionmentioning

confidence: 98%

Testosterone contributes to marked elevations in mean arterial pressure in adult male intrauterine growth restricted offspring

Ojeda¹,

Grigore²,

Yanes³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

130

178

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Our laboratory uses a model of intrauterine growth restriction (IUGR) induced by placental insufficiency in the rat to examine the developmental origins of adult disease. In this model only male IUGR offspring remain hypertensive in adulthood, revealing sex-specific differences. The purpose of this study was to determine whether testosterone with participation of the renin-angiotensin system (RAS) contributes to hypertension in adult male IUGR offspring. At 16 wk of age a significant increase in testosterone (346 Ϯ 34 vs. 189 Ϯ 12 ng/dl, P Ͻ 0.05) was associated with a significant increase in mean arterial pressure (MAP) measured by telemetry in IUGR offspring (147 Ϯ 1 vs. 125 Ϯ 1 mmHg, P Ͻ 0.05, IUGR vs. control, respectively). Gonadectomy (CTX) at 10 wk of age significantly reduced MAP by 16 wk of age in IUGR offspring (124 Ϯ 2 mmHg, P Ͻ 0.05 vs. intact IUGR) but had no effect in control (125 Ϯ 2 mmHg). A significant decrease in MAP in intact IUGR (111 Ϯ 3 mmHg, P Ͻ 0.05 vs. untreated intact IUGR) and castrated IUGR (110 Ϯ 4 mmHg, P Ͻ 0.05 vs. untreated CTX IUGR) after treatment with enalapril for 2 wk suggests a role for RAS involvement. However, the decrease in blood pressure in response to enalapril was greater in intact IUGR (⌬36 Ϯ 1 mmHg, P Ͻ 0.05) compared with CTX IUGR (⌬15 Ϯ 2 mmHg), indicating an enhanced response to RAS blockade in the presence of testosterone. Thus these results suggest that testosterone plays a role in modulating hypertension in adult male IUGR offspring with participation of the RAS.

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Section: Discussionmentioning

confidence: 98%

Testosterone contributes to marked elevations in mean arterial pressure in adult male intrauterine growth restricted offspring

Ojeda¹,

Grigore²,

Yanes³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

130

178

View full text Add to dashboard Cite

show abstract

“…In experimental animal models, castration reduced blood pressure in male rats with spontaneous (Martin et al 2005, Ojeda et al 2007 or fructose feeding-induced (Song et al 2004) hypertension. Testosterone has also been shown to inhibit L-type calcium channels via an AR-independent pathway, indicating nongenomic action of androgen on vasodilatation (Scragg et al 2004, Hall et al 2006.…”

Section: Androgens and Hypertensionmentioning

confidence: 99%

Effects of androgens on cardiovascular remodeling

Ikeda

Aihara

Yoshida³

et al. 2012

Journal of Endocrinology

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Androgens, the male sex hormones, exert various biological effects on many target organs through the transcriptional effects of the nuclear androgen receptor (AR). ARs are expressed not only in classical target organs, such as the brain, genital organs, bone, and skeletal muscles, but also in the cardiovascular system. Because the female sex hormones estrogens are wellknown to protect against cardiovascular disease, sex has been considered to have a significant clinical impact on cardiovascular mortality. However, the influence of androgens on the cardiovascular system has not been fully elucidated. To clarify this issue, we analyzed the effects of administration of angiotensin II and doxorubicin, an anticancer agent, in a loading model in male wild-type and AR-deficient mice. In this review, we focus on the actions of androgens as potential targets for the prevention of cardiovascular diseases in males.

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“…Testosterone is implicated to play a critical role in mediating hypertension in the spontaneously hypertensive rat (SHR) (13,19,25), and modulation of the RAS by testosterone exacerbates hypertension in male SHR (26). Upregulation of renal angiotensinogen expression by testosterone in the SHR may serve as one mechanism by which modulation of the RAS by testosterone contributes to the development of hypertension in the SHR (5, 7).…”

mentioning

confidence: 99%

Enhanced sensitivity to acute angiotensin II is testosterone dependent in adult male growth-restricted offspring

Ojeda¹,

Royals

Black

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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cental insufficiency results in intrauterine growth restriction (IUGR) and hypertension in adult male growth-restricted rats. Although renal ANG II and plasma renin activity do not differ between growthrestricted and control rats, blockade of the renin-angiotensin system (RAS) abolishes hypertension in growth-restricted rats, suggesting that the RAS contributes to IUGR-induced hypertension. Moreover, castration abolishes hypertension in growth-restricted rats, indicating an important role for testosterone. Therefore, we hypothesized that enhanced responsiveness to ANG II contributes to hypertension in this model of IUGR and that androgens may play a pivotal role in this enhanced response. Physiological parameters were determined at 16 wk of age in male rats pretreated with enalapril (40 mg·kg Ϫ1 ·day Ϫ1 ) for 1 wk. Baseline blood pressures were similar between growthrestricted (112 Ϯ 3 mmHg) and control (110 Ϯ 2 mmHg) rats; however, an enhanced pressor response to acute ANG II (100 ng·kg Ϫ1 ·min Ϫ1 for 30 min) was observed in growth-restricted (160 Ϯ 2 mmHg) vs. control (136 Ϯ 2 mmHg; P Ͻ 0.05) rats. Castration abolished the enhanced pressor response to acute ANG II in growthrestricted (130 Ϯ 2 mmHg) rats with no significant effect on blood pressure in controls (130 Ϯ 2 mmHg). Blood pressure was increased to a similar extent above baseline in response to acute phenylephrine (100 g/min) in control (184 Ϯ 5 mmHg) and growth-restricted (184 Ϯ 8 mmHg) rats, suggesting the enhanced pressor response in growthrestricted rats is ANG II specific. Thus, these results suggest that growth-restricted rats exhibit an enhanced responsiveness to ANG II that is testosterone dependent and indicate that the RAS may serve as an underlying mechanism in mediating hypertension programmed in response to IUGR. sex steroids; blood pressure; developmental programming ADVERSE INFLUENCES DURING early life can lead to an increased risk for cardiovascular and renal disease (4, 21). Using a model of reduced uterine perfusion in the pregnant rat, our laboratory has begun to elucidate the mechanisms linking intrauterine growth restriction (IUGR) and blood pressure (1). We previously reported that male growth-restricted offspring from reduced uterine perfusion dams exhibit a marked increase in arterial pressure in adulthood that is associated with a marked increase in intrarenal renin and angiotensinogen mRNA expression, and a marked increase in renal angiotensin I-converting enzyme (ACE) activity (9). However, despite these increases in intrarenal renin and angiotensinogen mRNA expression and intrarenal ACE activity, expression of intrarenal ANG II and its receptor, AT 1 R, are similar in hypertensive male growth-restricted rats compared with normotensive age-matched male control rats (9). Moreover, plasma renin activity, plasma renin substrate, and serum ACE activity are not altered in adult male growth-restricted rats relative to control (9, 22) suggesting that inappropriate activation of the systemic renin angiotensin system (RAS) is not obse...

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Castration reduces blood pressure and autonomic venous tone in male spontaneously hypertensive rats

Abstract: Accordingly we conclude that endogenous male sex steroids contribute to the elevated arterial and venous pressures observed in the SHR.

Cited by 26 publications

References 46 publications

Testosterone contributes to marked elevations in mean arterial pressure in adult male intrauterine growth restricted offspring

Testosterone contributes to marked elevations in mean arterial pressure in adult male intrauterine growth restricted offspring

Effects of androgens on cardiovascular remodeling

Enhanced sensitivity to acute angiotensin II is testosterone dependent in adult male growth-restricted offspring

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