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

Spironolactone, an aldosterone antagonist currently used in the treatment of hypertension, has numerous antiandrogenic side effects. Decreased production rates of testosterone in intact (N = 10) and hirsute (N = 6) women, respectively, were noted after short (7 days) or long-term (6 months) administration of the drug, 25 mg twice daily. A 50% diminution in the urinary 17-ketosteroid excretion was also observed after 6 months of therapy. Assessment of the treatment was done by the patients: a reduction in hair growth rate was initially observed after 3 to 4 months, followed by the appearance of a more downy type of new growth and a decrease in diameter of the hair shaft. It is concluded that this beneficial effect is obtained by a decrease in the testosterone production rate and probably through competitive inhibition of spironolactone and/or canrenone with the androgen receptor in human hair follicles.
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PMID:New therapeutic approach to the hirsute patient. 48 7

The objective of this study was to determine if males with a deficient androgen receptor would develop hypertension when crossed with a hypertensive parent. Female King-Holtzman rats (n = 15), heterozygous for the testicular feminization (Tfm) gene, were crossed with male spontaneously hypertensive rats (SHR), and blood pressure was measured weekly from 5-14 weeks in the F1 hybrid males. Approximately 50% of the F1 hybrid males were Tfm males and androgen receptor-deficient, and 50% were normal. Blood pressure in the parent King-Holtzman males, Tfms, and female rats was also followed for the same time period. The F1 normal male hybrids had a significantly higher (p less than 0.05) systolic blood pressure than the Tfm hybrid males after 12 weeks (195 +/- 8 versus 170 +/- 8 mm Hg, respectively). Blood pressure in the male and Tfm Holtzman rats was 120 +/- 5 mm Hg and 110 +/- 6 mm Hg, respectively. Castration lowered blood pressure by 38 mm Hg in the hybrid males and 27 mm Hg in the Tfm hybrids. Female F1 hybrids also showed a pressure rise above that of female Holtzman controls (155 +/- 6 mm Hg versus 110 +/- 6 mm Hg, p less than 0.01) but lower than the F1 males and Tfm hybrids. Ovariectomized females with testosterone implants did not show an elevation in blood pressure. Plasma electrolytes, norepinephrine, and cholesterol were not significantly different between normal and Tfm hybrid males. The results suggest that the presence of an androgen receptor and a testis-derived factor mediate the blood pressure rise in the hybrid males.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1991 Jun
PMID:Androgen receptor and the testes influence hypertension in a hybrid rat model. 204 56

The mechanisms resulting in the greater predisposition of male subjects towards hypertension were investigated in different strains of rats with genetic hypertension [spontaneously hypertensive rats of the stroke-prone strain (SHRSP) and spontaneously hypertensive rats (SHR)] and their respective normotensive controls. Blood pressure was reduced in young (9 weeks of age) hypertensive rats by (1) surgical castration, (2) treatment with the testosterone receptor antagonist cyproterone acetate (CPA), which does not elevate testosterone, or (3) with the testosterone receptor antagonist flutamide, which leads to a feedback elevation of gonadotrophic hormones and plasma testosterone. These treatments had no effect on high blood pressure in old hypertensive rats aged 25 weeks. Both androgen receptor antagonists attenuated high blood pressure development when given for the first 10 days after birth. These data clearly relate the sexual dimorphism of hypertension to testosterone produced during male brain maturation in the early phase of hypertension development. Testosterone appears not to contribute directly to the maintenance of high blood pressure in established hypertension.
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PMID:Sexual dimorphism of blood pressure in spontaneously hypertensive rats: effects of anti-androgen treatment. 252 10

The renin-angiotensin system plays an important role in blood pressure homeostasis, but the contribution of the type 2 angiotensin II receptor (AT2R) is still unclear. The reports that the AT2R gene has been mapped to the X chromosome in human and rat and the previous report of a gene, Bp3, on the X chromosome responsible for an increase in blood pressure have suggested that the rat AT2R gene (Agtr2) could be this gene. To elucidate whether Agtr2 is Bp3, Agtr2 was cloned. A simple sequence repeat in the 3'-flanking region of this gene was identified and used as a genetic marker to map Agtr2 to the X chromosome at 18.1 cM distal to the androgen receptor locus. This map position is outside the confidence interval reported for Bp3, demonstrating that Agtr2 cannot be Bp3. However, these data will enhance the research into the AT2R biology as well as the study of the X chromosome.
Hypertension 1995 Dec
PMID:Cloning, characterization, and genetic mapping of the rat type 2 angiotensin II receptor gene. 749 Jan 61

The clinical manifestations associated with hyperandrogenism, such as hirsutism and acne, are disturbing to most patients. In addition to correcting androgen-related problems, concerns such as contraception or other metabolic problems (for example, lipid/lipoprotein abnormalities, diabetes, hypertension) associated with these disorders and the effects of unopposed estrogen on the endometrium also need to be considered. Oral contraceptives are a therapeutic modality that may address these multiple problems. The potential mechanisms of action by which oral contraceptives correct excess androgen states include gonadotropin suppression, reduction of circulating androgens, increased androgen binding, suppression of adrenal androgen secretion and inhibition of 5 alpha-reductase, and androgen receptor binding. In normal women, there is good evidence that these actions occur with the use of oral contraceptives. Among women with anovulatory hyperandrogenic states, such as polycystic ovary syndrome, the response to oral contraceptives in each of these areas is somewhat more variable. However, oral contraceptive preparations that are more estrogen dominant appear to produce many of the desired effects. From a clinical standpoint, 60-100% of women with hirsutism improve on oral contraceptives; acne shows improvement in a high percentage of women as well. The use of oral contraceptives also reduces the risk of endometrial hyperplasia that may be associated with anovulatory states. Finally, current low-dose preparations containing the newer progestins (for example, norgestimate and desogestrel) appear to be either neutral, or perhaps beneficial, with respect to their metabolic impact.
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PMID:The role of oral contraceptives in the treatment of hyperandrogenic disorders. 782 33

Our laboratory has shown that the Y chromosome has a significant effect on blood pressure in the spontaneously hypertensive rat (SHR) model of hypertension and that the testes and androgen receptor contribute to the blood pressure rise. As an extension of our research, we have developed two new rat strains, SHR/a and SHR/y (F11) to study the Y chromosome. The objectives of the following research were 1) to study the blood pressure of rats with an SHR Y chromosome in a normotensive genetic background (SHR/y) or a normotensive Y chromosome in an SHR genetic background (SHR/a), 2) to determine the effect of male sex phenotype on the blood pressure of these rats, 3) to determine if testosterone replacement in castrated rats would restore blood pressure, and 4) to determine whether the Y chromosome from the SHR/y strain when crossed with a normotensive female can induce hypertension in androgen receptor-deficient male offspring. Blood pressure of male SHR/y rats was significantly higher than that of normotensive Wistar-Kyoto males (p < 0.01), and SHR/a males had significantly lower blood pressure compared with that of the parent SHR strain (p = 0.05). Testosterone replacement in castrated rats of both strains (SHR/a and SHR/y) restored blood pressure to control levels. Normotensive female King-Holtzman rats heterozygous for the testicular feminization gene were crossed with F11 SHR/a and SHR/y males.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1993 Jun
PMID:The hypertensive Y chromosome elevates blood pressure in F11 normotensive rats. 850 94

The spontaneously hypertensive rat (SHR) has a Y chromosome locus that increases blood pressure. This locus requires an androgen receptor and testosterone for maximum expression. Steroid sulfatase (STS) catalyzes the conversion of steroid sulfates to their active nonconjugated form. In some mammals the steroid sulfatase locus (Sts) is on the Y chromosome, although the rat Sts is on the X chromosome. We measured STS activity levels in SHR and normotensive Wistar Kyoto (WKY) males. SHR had significantly higher STS activity in testes, adrenal gland, liver, and hypothalamus. The Km values for STS in the two strains were not significantly different; thus, activity differences were likely due to differences in enzyme amounts. STS activity was measured in the backcross strains SHR/y and SHR/a to test and/or confirm a Y chromosome influence on STS. STS activity levels in these strains were intermediate between those of SHR and WKY. Because the blood pressures of SHR/y and SHR/a were also intermediate between SHR and WKY, the STS activity could be a secondary response to the hypertension. An alternative hypotheses is that a regulatory locus in addition to the structural locus is responsible for STS activity levels, and this regulatory locus is on the rat Y chromosome. Further study is needed to discriminate between these possibilities, and until the second hypothesis can be eliminated, the Sts locus or its modifier loci remain a potential component of the Y chromosome hypertensive locus.
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PMID:Steroid sulfatase and the Y chromosome hypertensive locus of the spontaneously hypertensive rat. 853 76

We report a 54-year-old man with X-linked bulbospinal muscular atrophy (BSMA) with bilateral abductor vocal cord paralysis. He noticed distal weakness in the lower limbs at age 20. In the following 18 years the weakness and atrophy of his leg muscles increased gradually. He has complained of stridors during respiratory tract infection and snored heavily during sleep since his age of 50. He was admitted to our hospital for the progressive stridors during meals. His two brothers were said to have similar complaints. Physical examination showed gynecomastia, hypertension and inspiratory stridor. Neurologic examination revealed distal muscular atrophy in his four extremities, especially more severe in bilateral lower limbs. Deep tendon reflexes were absent in all extremities. His tongue was slightly atrophic with fasciculation. Neurological diagnosis was made by family history, neurological findings, electromyography and a CAG repeat expansion in the androgen receptor gene. Lungs and diaphragm were normal on the chest radiograph. Cranial MRI including brain stem was also normal. Direct laryngoscopy showed a complete paralysis of both vocal cords in paramedian position. Tracheostomy was done right away; his respiratory distress showed prompt improvement after the tracheostomy. No previous report of bilateral vocal cord paralysis in BSMA has been found. Life expectancy in BSMA patients with vocal cord paralysis may be shortened because of respiratory distress or asphyxia. Of clinical importance is a careful assessment of vocal cord function in BSMA patients.
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PMID:[A case of X-linked bulbospinal muscular atrophy with bilateral abductor vocal cord paralysis]. 890 90

Anabolic steroids are synthetic derivatives of testosterone that were developed as adjunct therapy for a variety of medical conditions. Today they are most commonly used to enhance athletic performance and muscular development. Both illicit and medically indicated anabolic steroid use have been temporally associated with many subsequent defects within each of the body systems. Testosterone is the preferred ligand of the human androgen receptor in the myocardium and directly modulates transcription, translation, and enzyme function. Consequent alterations of cellular pathology and organ physiology are similar to those seen with heart failure and cardiomyopathy. Hypertension, ventricular remodeling, myocardial ischemia, and sudden cardiac death have each been temporally and causally associated with anabolic steroid use in humans. These effects persist long after use has been discontinued and have significant impact on subsequent morbidity and mortality. The mechanisms of cardiac disease as a result of anabolic steroid use are discussed in this review.
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PMID:The cardiac toxicity of anabolic steroids. 971 56

Males are at greater risk of cardiovascular and renal disease than are females. For example, male spontaneously hypertensive rats (SHR) have higher blood pressures than females. Androgens have been strongly implicated in the hypertension of male SHR, because castration attenuates the hypertension. This study determined whether the androgen receptor plays a role in hypertension in male SHR and whether testosterone alone can cause the hypertension or whether conversion to dihydrotestosterone is necessary. Male SHR, aged 10 weeks, were given the androgen receptor antagonist flutamide (8 mg/kg SC; n=8) or the 5alpha-reductase inhibitor finasteride (30 mg x kg(-1) x d(-1) SC; n=11) daily for 5 to 6 weeks. Control rats (n=10) received vehicle (20% benzyl benzoate or ethanol in castor oil). After 5 to 6 weeks, blood pressure (mean arterial pressure) and glomerular filtration rate were measured. Long-term flutamide treatment caused a reduction in mean arterial pressure (control 178+/-5 mm Hg; flutamide 159+/-3 mm Hg; P<0.01), but finasteride had no effect (180+/-5 mm Hg). There were no differences in glomerular filtration rate among the groups. These data indicate that hypertension in male SHR is mediated via the androgen receptor and does not require conversion of testosterone to dihydrotestosterone.
Hypertension 1999 Oct
PMID:Gender differences in hypertension in spontaneously hypertensive rats: role of androgens and androgen receptor. 1052 85


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