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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Men are generally at greater risk for cardiovascular disease than are women, particularly with regard to enhanced progression of hypertension and loss of renal function. Despite these gender differences in the progression of hypertension and renal disease in humans and animals, the mechanisms responsible are unknown. 2. Castration in males has been shown to slow the progression of hypertension and ameliorate the loss in renal function. When serum testosterone was measured in the developing male spontaneously hypertensive rat (SHR), the peak serum testosterone level at 12 weeks coincided with the time when differences in systolic blood pressure could be measured between intact male SHR and females or castrated male SHR. Ovariectomy does not affect blood pressure in female SHR but testosterone treatment of ovariectomized females for 5 weeks results in exacerbation of hypertension almost to the level found in intact male SHR. These data strongly suggest a role for androgens in mediating the gender differences in hypertension. 3. The mechanisms by which androgens could increase blood pressure are not known. We have recently shown that, at comparable renal perfusion pressures, there is a hypertensive shift in the pressure-natriuresis relationship in male SHR compared with females or castrated male SHR. Testosterone treatment of ovariectomized female SHR also causes a rightward shift in the pressure-natriuresis relationship. 4. We hypothesize that androgens increase arterial pressure by causing a hypertensive shift in the pressure-natriuresis relationship, either by having a direct effect to increase proximal tubular reabsorption or by activation of the renin-angiotensin system. We also hypothesize that the enhanced proximal tubular reabsorption leads to a tubuloglomerular feedback-mediated afferent vasodilation, which, in combination with the increase in arterial pressure, results in glomerular hypertension and renal injury.
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PMID:Role of androgens in mediating hypertension and renal injury. 1006 33

The tension in isolated ring preparations of the thoracic aortae from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) was measured isometrically to study the differences in testosterone-induced relaxation between WKY and SHR aortic rings. Testosterone (9 to 300 micromol/L) induced a concentration-dependent relaxation in both WKY and SHR aortic rings, and the relaxation induced by testosterone was greater in SHR than WKY. The relaxation induced by testosterone was significantly reduced by denudation of endothelium in SHR but not WKY. Indomethacin, an inhibitor of cyclooxygenase, and N(G)-nitro-L-arginine, an inhibitor of nitric oxide (NO) synthase, showed little influence on the relaxation induced by testosterone in both WKY and SHR aortic rings. Glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, significantly reduced the relaxation induced by testosterone in both WKY and SHR aortic rings, although the extent of reduction was greater in WKY than SHR. On the other hand, 4-aminopyridine, a selective inhibitor of voltage-dependent potassium channels, and tetraethylammonium, an inhibitor of calcium-activated potassium channels, significantly reduced the relaxation induced by testosterone in SHR but not WKY. These results suggest that the mechanisms of testosterone-induced vasorelaxation in both WKY and SHR involve, in part, ATP-sensitive potassium channels in the thoracic aortae and that in SHR aortic rings, testosterone may release endothelium-derived substances that may cause hyperpolarization of the cells by a mechanism that involves potassium channels. Moreover, the data show differences between WKY and SHR in the function of ATP-sensitive, voltage-dependent, and calcium-activated potassium channels.
Hypertension 1999 Dec
PMID:Different mechanisms for testosterone-induced relaxation of aorta between normotensive and spontaneously hypertensive rats. 1060 Nov 23

A sexual dimorphism in hypertension has been observed in both human and laboratory animal studies. The mechanisms by which male sex hormones regulate cardiovascular homeostasis are still not yet fully understood and represent the subject of this study. The possible involvement of androgen receptors in the development of hypertension and end-organ damage in transgenic rats harboring the mouse Ren-2 renin gene [TGR(mREN2)27] was studied. Male TGR(mREN2)27 rats were treated with the androgen receptor antagonist Flutamide starting at 4 wk of age. Also, an androgen receptor mutation (testicular feminization mutation [tfm]) was introduced in these rats by crossbreeding male TGR(mREN2)27 rats with tfm rats. The resulting offspring male rats that contain the tfm mutation are insensitive to androgens. Flutamide treatment or tfm mutation produced a significant attenuation of the development of hypertension. Besides a reduction in cardiac hypertrophy, urinary albumin excretion was blunted and no histologic characteristics of end-organ damage were observed in the kidney after Flutamide treatment. Testosterone levels increased 15-fold after Flutamide treatment and 2.7-fold by the tfm mutation. Also, plasma estrogens and luteinizing and follicle-stimulating hormones were significantly increased. Plasma renin concentrations and activity but not plasma angiotensinogen were reduced. Our results indicate that androgens contribute not only to the development of hypertension, but even more importantly to end-organ damage in TGR(mREN2)27 rats.
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PMID:Abolition of hypertension-induced end-organ damage by androgen receptor blockade in transgenic rats harboring the mouse ren-2 gene. 1239 37

The use of testosterone supplementation for elderly men has increased markedly over the last decade due to a recognized gradual decline in serum testosterone, which may lead to decreased bone mass, muscle strength, and libido. Testosterone supplementation is also used widely to treat some forms of erectile dysfunction, androgen deficiency, and infertility. However, long-term exogenous testosterone therapy has been associated with several complications, such as fluid retention, nitrogen retention, and hypertension. Due to these problems, alternate treatment modalities, involving more physiological and longer-acting systems for androgen delivery, have been pursued. Alginate-poly-L-lysine-encapsulated Leydig cell microspheres were used as a novel method for the delivery of testosterone in vivo. Encapsulated Leydig cells, which were stimulated with human chorionic gonadotropin, secreted high levels of testosterone in culture. Unencapsulated cells injected i.p. or s.c. failed to produce any testosterone levels, even with human chorionic gonadotropin stimulation. Castrated rats that were administered encapsulated Leydig cells i.p. or s.c. maintained a serum testosterone level between 0.23 and 0.51 ng/ml. Similar levels of testosterone were obtained for 43 d when the encapsulated Leydig cells were injected s.c. (0.28-0.48 ng/ml). Approximately 10% of a normal adult rat Leydig cell population was injected into each castrated animal; however, this resulted in serum testosterone levels of up to 40% of normal. Clinically, testosterone is usually delivered for supplementation and not for full replacement therapy. Therefore, the findings of this study suggest that microencapsulated Leydig cells may be a viable option as a therapeutic modality involving testosterone supplementation.
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PMID:Microencapsulation of Leydig cells: a system for testosterone supplementation. 1296 73

Male sex is an acknowledged risk factor for many forms of cardiovascular disease, and vascular disease prevalence patterns appear to be different in men versus women. The vascular properties of the principal mammalian androgen, testosterone, are complex and linked to dose, duration of exposure, presence of underlying vascular disease, and, possibly, biological sex. Data from isolated vessels and animal models suggest that pharmacological doses of testosterone, or its potent intracellular metabolite dihydrotestosterone, produce vasodilation. Testosterone's major effect on vascular beds at physiologic concentrations remains unclear, with documentation of both vasodilatory and vasoconstrictive actions. Results of various studies suggest that testosterone can alter vascular tone through both endothelium-dependent and endothelium-independent mechanisms in a variety of vascular beds and vessel types. Testosterone's endothelium-dependent effects are likely mediated at least in part through nitric oxide (NO) elaboration, whereas mechanisms of endothelium-independent effects involve 1 or more types of smooth muscle ion conductance channels. Data from clinical studies indicate that, in men, androgen replacement may provide beneficial effects when coronary artery disease is present. Conversely, in women, testosterone may augment existing hypertension, increase risk for cardiovascular events, or promote atherogenesis. However, it should be emphasized that most of these observations are anecdotal or come from small-scale clinical studies, and limited information is available in women. New research is required to understand the potential efficacy of androgen therapy, or lack thereof. This review focuses on current understanding of testosterone's physiological effects on vascular behavior and of testosterone's putative role in vascular health and disease.
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PMID:Testosterone as a modulator of vascular behavior. 1506 57

Recent clinical studies have reported that testosterone therapy reduces myocardial ischaemia in men with coronary artery disease, and the beneficial modulation of coronary vascular tone by testosterone has been proposed as an effector mechanism. Maintenance of a correct response to vasoconstrictive and vasodilatory agents is essential in the control of vascular tone. Endothelial dysfunction, most commonly manifested through an elevation in vascular tone, is implicated as an initiating factor in conditions such as hypertension and atherosclerosis. Increased sensitivity to vasoconstrictive stimuli is also proposed in the development of heart failure and hypertensive vascular remodelling, while increased coronary vascular reactivity to vasoconstrictive factors is likely further to restrict coronary blood flow through the partially occluded atherosclerotic vessel. Reduced vasodilatation and enhanced vasoconstriction can also lead to vasospasm and exacerbation of anginal symptoms. Testosterone is well known to elicit direct vasodilatation, but its influence upon responses induced by other vasoactive agents is less coherent, and may depend upon the underlying pathogenic process or gender. The aim of this review is to present the data obtained from both the patient and animal studies conducted to date, to ascertain any influence testosterone may have upon the regulation of vascular tone.
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PMID:The influence of testosterone upon vascular reactivity. 1524 19

In human internal mammary artery (IMA), testosterone induces vasodilation that shows marked variability among patients. We aimed to investigate the relationship of this variability with cardiovascular risk factors. Cumulative relaxations to testosterone after precontraction with KCl were examined in IMA segments from patients with identified cardiovascular risk factors such as hypercholesterolemia, diabetes, hypertension, smoking, age, gender, body mass index (BMI), and number of occluded vessels. Testosterone responses were significantly diminished in subjects with 3 compared with 1 risk factor. Hypercholesterolemia independently influenced testosterone responses by significantly decreasing its maximum, and smoking significantly decreased the sensitivity to testosterone. Thus, the variability observed in testosterone-induced vascular relaxations may in part be related to differences in risk factors present among the individuals studied.
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PMID:The relationship between risk factors and testosterone-induced relaxations in human internal mammary artery. 1561 72

Large artery stiffening increases cardiovascular risk and promotes isolated systolic hypertension which is more prevalent in elderly women than men. Variation in sex steroid levels between males and females and throughout life may modulate arterial stiffness. We hypothesized that sex steroids directly influence expression of important structural proteins which determine arterial biomechanical properties. Human aortic smooth muscle cells were incubated with physiological concentrations of 17beta-estradiol, progesterone, 17beta-estradiol and progesterone, or testosterone for 4 weeks. Collagen, elastin, and fibrillin-1 deposition was examined (histochemistry/immunohistochemistry). Gene and protein expression of 2 important matrix metalloproteinases (MMPs), MMPs 2 and 3, regulating matrix turnover was assessed. All sex steroids reduced collagen deposition relative to control (100%). However, the reduction was greater with female sex steroids than testosterone (control, 100%; 17beta-estradiol plus progesterone, 20+/-2%; testosterone 74+/-12%, P<0.001). Female sex steroids increased elastin deposition compared with control (control, 100%; 17beta-estradiol, 540+/-60%; progesterone, 290+/-40%; 17beta-estradiol plus progesterone, 400+/-80%, all P<0.01). The elastin/collagen ratio was >11-fold higher in the presence of 17beta-estradiol and progesterone compared with testosterone. Fibrillin-1 deposition was doubled in the presence of female sex steroids (17beta-estradiol plus progesterone) compared with testosterone (P<0.01). MMP-2 gene and protein expression was unaffected by any sex steroid. Testosterone increased both gene and protein expression of MMP-3 relative to both control and female sex steroids (P<0.01). This may contribute to degradation of elastic matrix proteins. In conclusion, female sex steroids promote an elastic matrix profile, which likely contributes to variation in large artery stiffness observed between sexes and with changes in hormonal status across the lifespan.
Hypertension 2005 Nov
PMID:Sex steroids modulate human aortic smooth muscle cell matrix protein deposition and matrix metalloproteinase expression. 1623 May 20

Males develop higher blood pressure than do females. This study tested the hypothesis that androgens enhance responsiveness to ANG II during the development of hypertension in New Zealand genetically hypertensive (NZGH) rats. Male NZGH rats were obtained at 5 wk of age and subjected to sham operation (Sham) or castration (Cas) then studied at three age groups: 6-7, 11-12, and 16-17 wk. Mean arterial blood pressure (MAP), heart rate (HR), and renal blood flow (RBF) measurements were recorded under Inactin anesthesia. These variables were measured after enalapril (1 mg/kg) treatment and during intravenous ANG II infusion (20, 40, and 80 ng/kg/min). Plasma testosterone was measured by ELISA. Angiotensin type 1 (AT1) receptor expression was assessed by Western blot analysis and RT-PCR. ANG II-induced MAP responses were significantly attenuated in Cas NZGH rats. At the highest ANG II dose, MAP increased by 40+/-4% in Sham vs. 22+/-1% in Cas NZGH rats of 16-17 wk of age. Similarly, renal vascular resistance (RVR) responses to ANG II were reduced by castration (209+/-20% in Sham vs. 168+/-10% in Cas NZGH rats at 16-17 wk of age). Castration also reduced MAP recorded in conscious NZGH rats of this age group. Testosterone replacement restored baseline MAP and the pressor and RVR responses to ANG II. Castration reduced testosterone concentrations markedly. Testosterone treatment restored these concentrations. Neither castration nor castration+testosterone treatment affected AT1 receptor mRNA or protein expression. Collectively, these data suggest that androgens modulate renal and systemic vascular responsiveness to ANG II, which may contribute to androgen-induced facilitation of NZGH rat hypertension.
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PMID:Androgens augment renal vascular responses to ANG II in New Zealand genetically hypertensive rats. 1646 40

Men are at greater risk of cardiovascular and renal diseases than women. Several hypertensive rat models also exhibit gender differences in blood pressure. Although the mechanisms responsible for these gender differences are not clear, androgens have been shown to promote hypertension. Testosterone is produced by Leydig cells under the regulation of catecholamines acting through both alpha- and beta-adrenoceptors. Some investigators have postulated a putative role of angiotensin II (Ang II) in modulating the action of gonadotropin in Leydig cells, inhibiting testosterone production. In the present work, we analysed the potential mechanism by which the testicular renin-angiotensin system (RAS) decreases the serum circulating levels of testosterone after the in vivo administration of the long-acting selective alpha(1)-adrenergic receptor antagonist doxazosin. RAS was analysed through assessment of the activity of its proteolytic regulatory enzymes. We can conclude that the testicular testosterone production, at least in rat, is regulated by catecholamines through a mechanism involving alpha(1)-adrenergic receptors and RAS, with a putative role for Ang III. Because doxazosin is usually used as a pharmacological therapy in the treatment of hypertension and benign prostatic hyperplasia, our results could also indicate that its benefits are due, at least in part, to decreased serum circulating levels of testosterone.
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PMID:In vivo administration of doxazosin in rats highly decreases serum circulating levels of testosterone through a mechanism involving the testicular renin-angiotensin system. 1757 49


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