Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic thromboembolic pulmonary hypertension (CTEPH) is an enigmatic disorder lacking signs, symptoms and classical risk factors for venous thromboembolism. The objective of the prospective case controlled study, carried out at the Pulmonary Hypertension Unit, University Hospital Vienna, Austria, was to investigate whether plasma FVIII is elevated in CTEPH patients. The study examined 122 consecutive patients diagnosed with CTEPH. Plasma FVIII was measured and compared with plasma FVIII of healthy controls (n = 82) and of patients with nonthromboembolic pulmonary arterial hypertension (PAH, n = 88). Results show that CTEPH patients had higher FVIII levels than controls (233 +/- 83IU/dl versus 123 +/- 40IU/dl, p < 0.0001) and PAH patients (158 +/- 61IU/dl, p < 0.0001). Plasma FVIII one year after surgery (212 +/- 94IU/dl) was statistically unchanged compared with preoperative values (FVIII: 226 +/- 88IU/dl, n = 25). FVIII > 230IU/dl was more prevalent in CTEPH patients (41%) than in controls (5%, p < 0.0001) and PAH patients (22%, p = 0.022). We can conclude that elevated plasma FVIII is the first prothrombotic factor identified in a large proportion of CTEPH patients.
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PMID:High prevalence of elevated clotting factor VIII in chronic thromboembolic pulmonary hypertension. 1295 4

Non-occlusive ureteral catheters were placed bilaterally in the renal pelves of 30 patients known to have hypertension. Samples of urine were collected under conditions of normal hydration, of urea-PAH-saline diuresis and, in some cases, mannitol diuresis. The samples were analyzed for indications of impaired flow of blood to the kidneys. Aortograms were obtained in all cases. This placement of non-occlusive catheters up into the renal pelves was felt to have caused only minimal disturbance of renal function, and was not accompanied by ureteral edema with the concomitant complications caused by occlusive catheters. Under conditions of normal hydration, leakage was insignificant. Of the 20 patients in whom urea-PAH-saline infusion revealed an ischemic pattern, 19 had an ischemic pattern under conditions of normal hydration. Since in the one exception an aortographic examination did not show a surgically reparable renal lesion, it may be inferred that the use of urea-PAH-saline diuresis is not essential in the preoperative evaluation of hypertensive renal disease. Correlation of the results of differential renal function studies and aortographic findings was possible in 19 of the 30 patients. Lack of correlation in the remaining 11 patients emphasized the importance of obtaining both types of study. Aortographic examination combined with differential renal function studies, using small ureteral catheters under conditions of normal hydration, should give the urologist a practical and yet accurate method of determining differential renal blood flow. If desired, further verification could be obtained by administering contrast medium and performing serial measurements of urine density.
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PMID:DIFFERENTIAL RENAL FUNCTION STUDY: AN AID IN PREOPERATIVE EVALUATION OF HYPERTENSIVE PATIENTS. 1433 97

Glomerular hyperfiltration, which is expected to occur after uninephrectomy, could potentially damage the non-transplanted donor kidney in living donor transplantation. We therefore prospectively measured renal function (inulin and PAH clearance), albumin excretion and blood pressure in the donors of 30 consecutive living donor kidney transplants before uninephrectomy (n = 29) and 1 week (n = 27) and 1 year (n = 16) after. Hyperfiltration was defined as: (post-nephrectomy inulin clearance)/(0.5 x pre-nephrectomy inulin clearance); hyperperfusion was defined in an analogous way for PAH clearance. Hyperfiltration averaged 128 +/- 5% [SEM] and hyperperfusion 133 +/- 6% 1 week after uninephrectomy. Hyperfiltration was nearly unchanged (126 +/- 7%) 1 year after nephrectomy, whereas hyperperfusion had significantly decreased to 118 +/- 8% (P < 0.02). There was no significant change in blood pressure after nephrectomy, and no new cases of hypertension were observed during the 1-year follow-up. The degree of hyperfiltration did not correlate with donor age. Microalbuminuria > 30 mg/24 h was found in two donors 1 week after nephrectomy (one of which normalized at 1 year) and in one additional donor 1 year after nephrectomy. The degree of hyperfiltration did not correlate with albumin excretion rate. In conclusion, no adverse consequences of hyperfiltration were demonstrable during the 1-year observation period, but the prognostic role of occasional microalbuminuria should be further investigated.
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PMID:Glomerular hyperfiltration after unilateral nephrectomy in living kidney donors. 1462 63

To determine the role of endogenous superoxide (O2-) in the kidney, we assessed renal hemodynamics and excretory function in gp91(PHOX) (a NAD(P)H oxidase subunit) gene knockout (KO) mice and compared these findings with those of wild-type (WT) strain C57BL/6 mice. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by PAH and inulin clearances respectively in anesthetized mice (n=8 in each group). There were higher baseline RBF (4.3+/-0.4 versus 2.5+/-0.2 mL/min per gram; P<0.002) and lower renal vascular resistance (RVR) (16+/-1.4 versus 29+/-2.3 mm Hg/mL/min per gram; P<0.0001) in KO compared with WT without a significant difference in mean arterial pressure (MAP) (67+/-2 versus 71+/-2 mm Hg) and GFR (0.66+/-0.09 versus 0.73+/-0.05 mL/min per gram) between the strains. Intravenous infusion of angiotensin II (Ang II) (2 ng/min per gram of body weight) for 30 minutes caused a lesser degree of decreases in RBF (-8% versus -33%) and of increases in RVR (+73% versus +173%) in KO compared with WT. GFR was increased (43%) in KO but not in WT during Ang II infusion. Urinary excretion of nitrate/nitrite was higher in conscious KO (n=5) than in WT (n=5), indicating an increase in nitric oxide bioavailability that could be the cause of high RBF and low RVR in KO. These data indicate that gp91(PHOX), a subunit of NAD(P)H oxidase, plays a regulatory role in the maintenance of renal vascular tone. These results also suggest that the mechanism of Ang II-mediated renal vascular action involves concomitant generation of O2-.
Hypertension 2004 Feb
PMID:Assessment of renal functional phenotype in mice lacking gp91PHOX subunit of NAD(P)H oxidase. 1471 66

Chronic pulmonary hypertension (PHT) is characterized by permanently increased pulmonary artery pressure. Diagnostic criteria are a mean pulmonary arterial pressure above 25 mmHg at rest and above 30 mmHg during exercise. Pulmonary arterial hypertension is characterized by progressive obliteration of the pulmonary vascular bed, which results in progressive right heart failure and death. Pathologic processes behind the complex vascular changes associated with PHT include vasoconstrictor/vasodilator imbalance, thrombosis, misguided angiogenesis and inflammation. The function of the pulmonary endothelium is altered with decreased production of vasodilators such as prostacyclin and nitric oxide and an increased production of endothelins, finally resulting in pulmonary vascular remodelling. A new diagnostic classification of pulmonary hypertension (PHT) was proposed at the World Health Organization (WHO) Pulmonary Hypertension Meetings held in Evian in 1998 and in Venice in 2003. This classification reflects recent advances in the understanding of pulmonary hypertensive diseases. Depending on the underlying disease and the localization of the vascular lesion, five different subgroups of PHT are formed. An exact diagnostic classification is necessary for application of the current treatment options for the different forms of PHT. Target of therapy is besides avoiding local thrombosis by anticoagulation and treatment of vasoconstriction, the prevention of vascular remodelling. For patients with advanced pulmonary arterial hypertension (PAH; NYHA stages III and IV) treatment with prostanoids (inhalative, oral, subcutaneous or intravenous), with endothelin-receptor antagonists or with a phosphodiesterase inhibitor can be indicated. Whether initial or adjunct combined therapy provides additional clinical benefits to patients with severe pulmonary arterial hypertension needs further investigation, but first results are promising.
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PMID:[Pulmonary hypertension. Pathophysiology and current concepts of medication therapy]. 1527 94

New drugs for pulmonary arterial hypertension have shown efficacy in randomized controlled trials. Endothelin receptor antagonists (ERA) and prostanoids are most important for clinical practice. Bosentan represents the first approved orally active therapy for PAH. Besides its hepatotoxicity it is mostly well tolerated. The first approved prostanoid, epoprostenol, is currently first choice only for decompensated right heart failure in PAH. It has to be delivered continuously intravenously and is prone to complications, side effects and very high costs. Alternatively, subcutaneous treprostinil can be applied. It is less risky and expensive but may cause local pain at the infusion site. Inhaled iloprost combines the features of a prostanoid with pulmonary and intrapulmonary selectivity. Alternatively, iloprost is being used as continuous intravenous infusion. The phosphodiesterase-5 inhibitor sildenafil was effective in two randomized controlled trials but has not been approved for PAH therapy.
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PMID:[Therapy of pulmonary arterial hypertension]. 1570 89

Primary pulmonary arterial hypertension is a rare lethal disease that typically presents radiographically with enlarged central pulmonary arteries, pruning of the peripheral vasculature, and cardiomegaly but clear lung fields. Although it is a disease of unknown etiology, primary PAH has been associated with anorexigen use. We present a case of pulmonary arterial hypertension in a woman with a history of fenfluramine and phentermine use who presented with diffuse micronodules on computed tomography scan. Lung biopsy confirmed the micronodules were radiographic manifestations of extensive diffuse plexogenic arterial lesions. This report represents an unusual radiographic presentation of anorexigen related pulmonary arterial hypertension, and to our knowledge, the first case reported as presenting with diffuse micronodules on high resolution computed tomography scan.
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PMID:Primary pulmonary arterial hypertension presenting as diffuse micronodules on CT. 1574 74

Mutations in the bone morphogenetic protein type II receptor gene (BMPR2) are the major genetic cause of familial pulmonary arterial hypertension (FPAH). Although smooth muscle cell proliferation contributes to the vascular remodeling observed in PAH, the role of BMPs in this process and the impact of BMPR2 mutation remains unclear. Studies involving normal human pulmonary artery smooth muscle cells (PASMCs) suggest site-specific responses to BMPs. Thus, BMP-4 inhibited proliferation of PASMCs isolated from proximal pulmonary arteries, but stimulated proliferation of PASMCs from peripheral arteries, and conferred protection from apoptosis. These differences were not caused by differential activation of BMP signaling pathways because exogenous BMP-4 led to phosphorylation of Smad1, p38(MAPK), and ERK1/2 in both cell types. However, the proproliferative effect of BMP-4 on peripheral PASMCs was found to be p38MAPK/ERK-dependent. Conversely, overexpression of dominant-negative Smad1 converted the response to BMP-4 in proximal PASMCs from inhibitory to proliferative. Furthermore, we confirmed that proximal PASMCs harboring kinase domain mutations in BMPR2 are deficient in Smad signaling and are unresponsive to the growth suppressive effect of BMP-4. Moreover, we show that the pulmonary vasculature of patients with familial and idiopathic PAH are deficient in the activated form of Smad1. We conclude that defective Smad signaling and unopposed p38(MAPK)/ERK signaling, as a consequence of mutation in BMPR2, underlie the abnormal vascular cell proliferation observed in familial PAH.
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PMID:Dysfunctional Smad signaling contributes to abnormal smooth muscle cell proliferation in familial pulmonary arterial hypertension. 1592 25

Pulmonary hypertension is a rare disease of the pulmonary vasculature defined as a mean pulmonary artery pressure >25 mmHg at rest or 30 mmHg with exercise. Recent therapies such as epoprostenol, bosentan and sildenafil are directed at the arterial vascular bed, causing vasodilatation and reducing pulmonary vascular resistance. However idiopathic pulmonary artery hypertension (IPAH) occurs predominantly in women, with three times the incidence compared to men and this suggests that sex hormones may be involved in the pathogenesis. 17beta -oestradiol is a pulmonary vasodilator, proposed to act via an endothelium-dependant pathway, involving nitric oxide (NO) and has also been shown to alter responses to hypoxia. Progesterone is also a pulmonary vasodilator but differs from 17beta-oestradiol in having endothelial-dependant and independent processes implicated. Interestingly testosterone has been shown to be a vasodilator in both the coronary and pulmonary circulation with a mechanism of action involving calcium channel blockade of the vascular smooth muscle and without endothelial involvement. In clinical trials testosterone confers symptomatic benefits in patients with coronary heart disease and heart failure, acting as a vasodilator. These observations lend support to the notion that testosterone could be a potential treatment for patients with PAH as vasodilator therapy remains the mainstay of treatment. Other potential beneficial effects of testosterone in the pulmonary circulation include immuno-modulation, altering expression of cytokines and an anti-thrombotic action. In this review the influence of sex hormones on the pulmonary vasculature will be discussed, with specific focus on pulmonary hypertension and the potential treatment of this condition.
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PMID:The influence of sex hormones on pulmonary vascular reactivity: possible vasodilator therapies for the treatment of pulmonary hypertension. 1647 72

Heterozygous germline mutations in the gene encoding the bone morphogenetic protein type II (BMPR-II) receptor underlie the majority (>70%) of cases of familial pulmonary arterial hypertension (FPAH), and dysfunction of BMP signaling has been implicated in other forms of PAH. The reduced disease gene penetrance in FPAH indicates that other genetic and/or environmental factors may also be required for the clinical manifestation of disease. Of these, the serotonin pathway has been implicated as a major factor in PAH pathogenesis. We investigated the pulmonary circulation of mice deficient in BMPR-II (BMPR2(+/-) mice) and show that pulmonary hemodynamics and vascular morphometry of BMPR2(+/-) mice were similar to wild-type littermate controls under normoxic or chronic hypoxic (2- to 3-week) conditions. However, chronic infusion of serotonin caused increased pulmonary artery systolic pressure, right ventricular hypertrophy, and pulmonary artery remodeling in BMPR2(+/-) mice compared with wild-type littermates, an effect that was exaggerated under hypoxic conditions. In addition, pulmonary, but not systemic, resistance arteries from BMPR2(+/-) mice exhibited increased contractile responses to serotonin mediated by both 5-HT2 and 5-HT1 receptors. Furthermore, pulmonary artery smooth muscle cells from BMPR2(+/-) mice exhibited a heightened DNA synthesis and activation of extracellular signal-regulated kinase 1/2 in response to serotonin compared with wild-type cells. In vitro and in vivo experiments suggested that serotonin inhibits BMP signaling via Smad proteins and the expression of BMP responsive genes. These findings provide the first evidence for an interaction between BMPR-II-mediated signaling and the serotonin pathway, perturbation of which may be critical to the pathogenesis of PAH.
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PMID:Serotonin increases susceptibility to pulmonary hypertension in BMPR2-deficient mice. 1649 88


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