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

The binding and internalization of recombinant human renin and prorenin (2500 microU/mL) and the activation of prorenin were studied in neonatal rat cardiac myocytes and fibroblasts cultured in a chemically defined medium. Surface-bound and internalized enzymes were distinguished by the addition of mannose 6-phosphate to the medium, by incubating the cells both at 37 degrees C and 4 degrees C, and by the acid-wash method. Mannose 6-phosphate inhibited the binding of renin and prorenin to the myocyte cell surface in a dose-dependent manner. At 37 degrees C, after incubation at 4 degrees C for 2 hours, 60% to 70% of cell surface-bound renin or prorenin was internalized within 5 minutes. Intracellular prorenin was activated, but extracellular prorenin was not. The half-time of activation at 37 degrees C was 25 minutes. Ammonium chloride and monensin, which interfere with the normal trafficking and recycling of internalized receptors and ligands, inhibited the activation of prorenin. Results obtained with cardiac fibroblasts were comparable to those in the myocytes. This study is the first to show experimental evidence for the internalization and activation of prorenin in extrarenal cells by a mannose 6-phosphate receptor-dependent process. Our findings may have physiological significance in light of recent experimental data indicating that angiotensin I and II are produced at cardiac and other extrarenal tissue sites by the action of renal renin and that intracellular angiotensin II can elicit important physiological responses.
Hypertension 1997 Dec
PMID:Mannose 6-phosphate receptor-mediated internalization and activation of prorenin by cardiac cells. 940 58

Acute and chronic angiotensin (Ang) II hypertension are reported to have different mechanisms that involve differential contributions of the peripheral vasculature and the nervous system. Acute Ang II hypertension is mediated primarily by Ang acting at vascular smooth muscle, whereas chronic Ang II hypertension appears to have a neural component. In our experiments, the transition from a peripheral to a neural effect occurs over 10 hr of Ang II infusion in rats. To identify the role of the central nervous system in this transition, we measured Fos immunoreactivity, an indicator of neural activity, in the nucleus of the solitary tract (NTS), caudal ventrolateral medulla (CVL) and rostral ventrolateral medulla (RVL) in normal, sinoaortic denervated (SAD) and sham SAD rats after 2- or 18-hr Ang II infusion (50 ng/kg/min intravenously). Vehicle (5% dextrose) was infused in normal rats as control. Comparable increases in arterial pressure were produced by 2- and 18-hr Ang II infusion in all groups. Fos was increased in the NTS in sham SAD rats by 2- and 18-hr Ang II infusion (P < .05 vs. vehicle control). In the CVL, only 2-hr Ang II infusion was associated with increased Fos in normal and sham SAD rats (P < .05 vs. vehicle control) but not in SAD rats. In the RVL, 18-hr Ang II infusion elevated Fos in all groups (P < .05 vs. vehicle control). Activation of NTS during Ang II infusion is baroreceptor mediated and independent of infusion duration. Acute Ang II infusion produced a baroreceptor-mediated activation of the CVL, a region associated with baroreflex sympathoinhibition. Chronic Ang II infusion produced a baroreceptor-independent activation of the RVL, a brain area associated with sympathoexcitation, suggesting a centrally mediated increase in sympathetic outflow that may be associated with chronically infused Ang II.
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PMID:Fos-like immunoreactivity in the medulla after acute and chronic angiotensin II infusion. 949 79

Endometriosis is probably a complex trait, like diabetes, hypertension or asthma, which implies that the disease is caused by an interaction between multiple genes and the environment. This paper reviews the evidence, in both human and nonhuman primates, that supports the theory of a genetic basis to endometriosis. The OXEGENE study, which aims to identify susceptibility genes in endometriosis through linkage analysis, is also described. DNA is being collected from families containing at least two sisters with surgically confirmed revised American Fertility Society stage III and IV disease to carry out a genome-wide search for susceptibility genes. Candidate genes involved in galactose metabolism and dioxin detoxification are also being analyzed. The identification of genes conferring susceptibility to endometriosis may lead to a better understanding of disease etiology and, in time, improved therapeutic strategies and diagnostic methods.
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PMID:The genetics of endometriosis. 956 59

During the last decade there were extensive investigations in clinical and molecular andrology with emphasis on assisted reproduction, micromanipulation techniques of gametes, sperm/egg interaction, male contraception, diabetes mellitus, varicocele, andropause versus menopause, sexual dysfunction, associated hypertension/stress, prostatic carcinoma and molecular parameters of male reproduction. Sperm hyperactivation is a required step in capacitation sequence. Sperm motility is measured by videotape to evaluate the Straight Line Velocity (microm/s) (VSLI). Fertilization/embryonic development results from single sperm transfer (S-MIST) and multiple sperm transfer. Fertilization/embryo development is achieved by injection of immotile sperm into the perivitelline space. To assess sperm viability, a supravital stain suitable for use in combination with immunofluorescent assay, Hoeschst 33258, is used. The dye fluoresces with an intense blue when bound to DNA. To assess sperm plasma membrane integrity, a hypo-osmotic swelling test (HOST) is performed, using fluoresceinated D-mannose enriched albumin (FITC-DMA). The ability of sperm to swell under hypo-osmotic conditions indicates an intact membrane. A human protein, C-peptide, thought to be a useless byproduct of insulin may protect against devastating heart and nerve damage that diabetes causes. Human diabetics may benefit from the substance. Over 15 million Americans have diabetes, in which blood sugar levels rise out of control. There are two types of diabetics: Type I diabetics produce no insulin, the hormone that regulates blood sugar. Type II diabetics are unable to use their insulin properly. Diabetics are at great risk of heart disease and nerve damage, as arteries throughout the body leak and nerve-cell impulses fail. C-peptide is a byproduct of insulin production; it can be produced by the body or synthetically. Production of this protein is not induced by insulin, so diabetics who take insulin do not get C-peptide with it. Varicocele occurs unilaterally on the left side in 78% to 93% of men. Typically the presence of a varicocele is associated with an abnormal semen analysis (sperm density and morphology) and a decreased testicular volume on the affected side. Impaired sperm motility occurs in 89.5% of all varicocele patients. Varicocele ligation improves semen parameters in two thirds of patients. A few studies on andropause included sexual dysfunction, hormonal changes, medical/psychological correlates of impotence, ostenopenia/osteoporosis and bone loss; indices of bone remodeling, testosterone supplementation, androgen, negative feedback and hypothalamo-pituitary-testicular axis. Prostatic cancer is the second leading cause of cancer death for men between the ages of 60 and 80. Early detection involves a simple blood test for prostate specific antigen (PSA). Regular screening and early detection are essential. This is an important test because a high antigen count can be the only symptom. Since no screening is 100% accurate, physicians recommend both a PSA blood test and a physical examination. Although heredity plays a major role in whether a man will develop prostate cancer, men who lead healthy lives can dramatically reduce their chances of cancer: low-fat diet, eating plenty of fruits and vegetables and not smoking. Recent advances in molecular andrology include peptide hormone binding proteins; gonadotropin-releasing hormone (GnRH) agonists/antagonists analog; gonadotropins/their receptors; growth factors/reproduction; peptides as intratesticular regulators; molecular cloning of reproductive proteins/peptides. Gene cloning is applied for characterization/expression of genes coding. The interaction of gp120 with CD4 receptor plays a role in syncytium formation, apoptosis and CD4 cell deletion in human immunodeficiency virus (HIV) infection. The recombinant V3 peptide of fragment 307-330 of HIV-1 can induce sperm head agglutination. The generation process of react
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PMID:Recent advances in clinical/molecular andrology. 958 57

Renovascular hypertension resulting from renal artery stenosis is a potentially curable form of secondary hypertension. Although uncommon in the general hypertensive population, the prevalence of renovascular hypertension rises in selected groups of hypertensive patients. Because of the possibility of cure, screening measures for renal artery stenosis are warranted in hypertensive patients with clinical features suggestive of renovascular disease. For a long time, angiography has been considered the 'gold standard' in screening for arterial stenosis. However, it is invasive and associated with inherent morbidity. Thus, less invasive screening measures with high diagnostic sensitivity and specificity are currently being sought. Magnetic resonance angiography and captopril renal scintigraphy are safer alternatives to angiography, but are expensive and not widely available. Duplex ultrasound is more widely available and provides both anatomic and functional assessment of renal artery stenosis; however, sensitivity and specificity vary considerably among different laboratories. Echo-enhanced duplex ultrasound using the galactose-based agent Levovist(R) produces higher quality images of the renal artery than conventional color Doppler, while significantly reducing mean examination time and improving diagnostic confidence. In addition, Levovist does not compromise the safety of duplex ultrasound. Other advances in Doppler imaging techniques that may improve ultrasound sensitivity and specificity in detection of renal artery stenosis are power Doppler, echo-enhanced harmonic spectral Doppler imaging, and echo-enhanced harmonic power Doppler imaging.
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PMID:Diagnosis of renal artery stenosis and renovascular hypertension. 967 31

1. Recent animal evidence suggests that aldosterone, like angiotensin II, may possess detrimental autonomic modulating properties. Aldosterone has been shown to impair the baroreflex response in animal models. This study is designed to test the hypothesis that aldosterone directly attenuates the baroreflex in vivo in man.2. Fourteen healthy male volunteers [mean age (S.D.) 25 (9) years] received intravenous d-aldosterone (12 pmol.min-1.kg-1) and 5% dextrose (vehicle) in a double-blind crossover fashion, co-infused with incremental doses of intravenous phenylephrine and sodium nitroprusside. Aldosterone had no significant effect on resting blood pressure, heart rate or baroreflex response to sodium nitroprusside. However, reflex responses to phenylephrine were impaired with aldosterone (P<0.01) while blood pressure responses were unaltered. Baroreflex sensitivity was significantly blunted in the aldosterone group [8.36+/-2.19 versus 10.12+/-2.27 ms/mmHg; P<0. 04].3. This study confirms previous observations from animal models that aldosterone impairs the baroreflex response. High aldosterone levels may contribute to the baroreflex dysfunction in cardiovascular diseases such as hypertension and heart failure.
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PMID:Aldosterone blunts the baroreflex response in man. 983 88

The epithelial Na+ channel (ENaC) complex is composed of three homologous subunits: alpha, beta and gamma. Mutations in ENaC subunits can increase the number of channels on the cell surface, causing a hereditary form of hypertension called Liddle's syndrome, or can decrease channel activity, causing pseudohypoaldosteronism type I, a salt-wasting disease of infancy. To investigate surface expression, we studied ENaC subunits expressed in COS-7 and HEK293 cells. Using surface biotinylation and protease sensitivity, we found that when individual ENaC subunits are expressed alone, they traffic to the cell surface. The subunits are glycosylated with high-mannose oligosaccharides, but seem to have the carbohydrate removed before they reach the cell surface. Moreover, subunits form a complex that cannot be disrupted by several non-ionic detergents. The pattern of glycosylation and detergent solubility/insolubility persists when the N-teminal and C-terminal cytoplasmic regions of ENaC are removed. With co-expression of all three ENaC subunits, the insoluble complex is the predominant species. These results show that ENaC and its family members are unique in their trafficking, biochemical characteristics and post-translational modifications.
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PMID:Cell surface expression and biosynthesis of epithelial Na+ channels. 984 84

-Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats from 5 to 9 weeks of age received a regular or high salt diet and concomitantly an intracerebroventricular infusion of the angiotensin type 1 blocker losartan (1 mg. kg-1. d-1) or antibody Fab fragments, which bind ouabain and related steroids with high affinity, or gamma-globulins as control (200 microg/d for both). At 9 weeks of age, blood pressure (BP), heart rate (HR), central venous pressure, and renal sympathetic nerve activity were recorded in conscious rats at rest and in response to air stress and to intracerebroventricular alpha2-agonist guanabenz (50 microg) and ouabain (0.5 microg). Baroreflex function was assessed by acute volume expansion with intravenous 5% dextrose and ramp changes of BP by +/-50 mm Hg induced by intravenous phenylephrine and sodium nitroprusside. In Dahl S but not R rats, high salt significantly increased BP and HR; enhanced BP, HR, and renal sympathetic nerve activity responses to air stress and guanabenz; and attenuated cardiopulmonary and arterial baroreflex control of renal sympathetic nerve activity and HR. Both losartan and Fab fragments prevented these responses to high salt to a similar extent in Dahl S rats but had no effect in Dahl R rats on high salt. Sympathoexcitatory responses to ouabain were attenuated in Dahl S on high versus regular salt and were abolished in Dahl R or S treated with losartan or Fab fragments. Consistent with previous studies in SHR, the present data indicate that in Dahl S on high salt, both brain "ouabain" and angiotensin II contribute to decreased sympathoinhibition and increased sympathoexcitation, impairment of baroreflex, and therefore hypertension.
Hypertension 1998 Dec
PMID:Both brain angiotensin II and "ouabain" contribute to sympathoexcitation and hypertension in Dahl S rats on high salt intake. 985 68

Intra-arterial infusion of insulin in physiological doses causes forearm vasodilation which is augmented by co-infusion of D-glucose, leading us to speculate that local insulin-mediated vasodilation may depend on insulin-mediated glucose uptake. We have examined the relationship between whole-body insulin sensitivity and forearm vasodilation in response to local infusion of insulin/glucose, thus avoiding any confounding effects of sympathetic stimulation on peripheral blood flow. Eighteen healthy, normotensive male volunteers (age, 26+/-5.4 years) attended on two separate occasions for measurement of: (1) whole-body insulin sensitivity with use of the hyperinsulinemic euglycemic clamp; (2) forearm vasodilation in response to an intra-arterial infusion of insulin/glucose with use of bilateral venous occlusion plethysmography. Insulin-mediated glucose uptake (M) for the group (mean+/-SD) was 10.0+/-2.2 mg. kg-1. min-1, and the percentage change in forearm blood flow ratio (%FBFR) for the group (median, interquartile range) was 28.2% (13.6, 48.6). In univariate analysis, M was significantly correlated with %FBFR (rs=0.60, P<0.05), but not with body mass index (BMI) (rs=-0. 42), age (r=-0.39) or mean arterial pressure (r=0.13). In multiple regression analysis, %FBFR remained a significant independent predictor of M (R2 (adj)=0.48, t=3.23, P<0.01) in a model involving BMI, age, and blood pressure. These data support the concept of a significant functional relationship between insulin's metabolic and vascular actions, possibly at an endothelial level.
Hypertension 1999 Jan
PMID:Insulin-mediated vasodilation and glucose uptake are functionally linked in humans. 993 Nov 64

Sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), is a well-tolerated and highly effective treatment for erectile dysfunction. The mechanism of action of sildenafil depends on activation of the nitric oxide (NO)-cGMP pathway during sexual stimulation, which results in corpus cavernosal smooth muscle relaxation and penile erection. Endogenously derived NO is also involved in blood pressure regulation through its effect on basal vascular tone, which is mediated by cGMP levels. Organic nitrates and NO donors exert their therapeutic effects on blood pressure and vascular smooth muscle by the same mechanism as endogenous NO. Since both sildenafil and organic nitrates exert their pharmacologic effects via increases in cGMP concentrations, a double-blind, placebo-controlled, crossover study was undertaken to investigate the effects of sildenafil coadministered with glyceryl trinitrate on blood pressure and heart rate in healthy male subjects. The hemodynamic effects of sildenafil were also evaluated in a second placebo-controlled crossover study in men with hypertension who were taking the calcium antagonist amlodipine, which has a mechanism of action that does not involve the cGMP pathway. In the first crossover study, subjects were treated with oral sildenafil (25 mg, 3 times a day for 4 days) or placebo and then challenged on day 4 with a 40-minute, stepwise, intravenous infusion of glyceryl trinitrate (0.5 mg/mL in 5% dextrose at an initial infusion rate of 2.5 microg/min and doubling every 5 minutes to a maximum rate of 40 microg/min) 1 hour after taking sildenafil or placebo. On day 5, subjects received a sublingual glyceryl trinitrate tablet (500 microg) 1 hour after taking 25 mg of sildenafil or placebo. During sildenafil treatment, the subjects were significantly less tolerant of intravenously administered glyceryl trinitrate than during placebo treatment, based on the occurrence of a >25 mm Hg decrease in blood pressure or the incidence of symptomatic hypotension (p <0.01). When a sublingual glyceryl trinitrate tablet was administered on day 5, a 4-fold greater decrease in systolic blood pressure was observed for the subjects during the sildenafil treatment period than during the placebo treatment period. The changes in heart rate were negligible during both glyceryl trinitrate challenges. In conclusion, sildenafil potentiated the hypotensive effects of glyceryl trinitrate, an organic nitrate. Thus, sildenafil administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is contraindicated. In the second crossover study, men with hypertension, who were taking 5 or 10 mg/day of amlodipine, received a single oral dose of 100 mg sildenafil or placebo. Coadministration of sildenafil did not significantly affect the pharmacokinetics of amlodipine. In the 4 hours after dosing, differences in the mean maximum change from baseline in supine systolic and diastolic blood pressures between the sildenafil plus amlodipine and the placebo plus amlodipine treatment periods were -8 mm Hg and -7 mm Hg, respectively (p < or =0.002). The mean maximum supine heart rate increased 2.1 beats/min during sildenafil plus amlodipine treatment and decreased 1.5 beats/min during placebo plus amlodipine treatment (p <0.02). The adverse events in this study were predominantly mild or moderate and did not cause discontinuation of treatment. Adverse events considered to be related to sildenafil treatment included headache, nausea, and dyspepsia. In patients with hypertension who were taking amlodipine therapy, sildenafil produced additive, but not synergistic, reductions in blood pressure. The difference in the mean maximum change from baseline in blood pressure between sildenafil plus amlodipine and placebo plus amlodipine was comparable to the decrease in blood pressure reported for healthy men taking sildenafil alone. (ABSTRACT TRUNCATED)
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PMID:Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. 1007 39


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