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

Idiopathic pulmonary arterial hypertension (IPAH) is a pulmonary vasculopathy of unknown aetiology. Dyspnoea, peripheral airway obstruction and inefficient ventilation are common in IPAH. Data on respiratory muscle function are lacking. This prospective single-centre study included 26 female and 11 male patients with IPAH in World Health Organization functional classes II-IV. Mean+/-SD pulmonary artery pressure was 48.6+/-16.9 in females and 53.1+/-22.9 mmHg in males; cardiac output was 3.7+/-1.3 and 4.2+/-1.7 L x min(-1). Maximal inspiratory pressure (PI,max) was lower in the female patients than in 20 controls (5.3+/-2.0 versus 8.2+/-2.0 kPa). In the male patients, PI,max was lower than in 25 controls (6.8+/-2.2 versus 10.5+/-3.7 kPa). Maximal expiratory pressure (PE,max) was lower in the female patients than in controls (6.2+/-2.6 versus 9.5+/-2.1 kPa), and in male patients as compared to controls (7.1+/-1.6 versus 10.3+/-3.9 kPa). There was no correlation between PI,max or PE,max and parameters of pulmonary haemodynamics or exercise testing. The ratio of mouth occlusion pressure within the first 0.1 s of inspiration and PI,max was higher in IPAH than in controls (females 0.067+/-0.066 versus 0.021+/-0.008; males 0.047+/-0.061 versus 0.023+/-0.016). In conclusion, this study provides the first evidence of inspiratory and expiratory muscle weakness in idiopathic pulmonary arterial hypertension. The pathomechanisms and the prognostic significance should be further investigated.
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PMID:Respiratory muscle dysfunction in idiopathic pulmonary arterial hypertension. 1564 Mar 33

Idiopathic pulmonary arterial hypertension is a rare but serious and life-threatening disease that leads to right heart failure and death within 2.8 years without specific treatment. This review focuses on the stable prostacyclin analog iloprost, its biologic action and pharmacology and, finally, on its clinical development, efficacy and safety in patients with idiopathic pulmonary arterial hypertension, which led to its approval for this indication. Furthermore, this review assesses the role of iloprost compared with other newly developed drugs, such as the endothelin receptor antagonist bosentan and the phosphodiesterase-5 inhibitor sildenafil, as well as other modes of application of prostacyclin and its analogs for the treatment of idiopathic pulmonary arterial hypertension. Based on the different modes of action of these substances, a combination of these treatments could be most promising for the future.
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PMID:Iloprost for idiopathic pulmonary arterial hypertension. 1585 95

Idiopathic pulmonary arterial hypertension (formerly primary pulmonary hypertension) can affect more than one member of the same family. In the past 25 years scientists have exposed the inheritance pattern and a major element of the molecular basis for inherited pulmonary arterial hypertension. Familial pulmonary arterial hypertension is inherited as an autosomal dominant trait with incomplete penetrance (i.e., several individuals inherit a predisposition to the disease, but never express it). Mutations in the gene that codes for bone morphogenetic protein receptor type II (BMPR-II) are a major predisposition for the development of pulmonary arterial hypertension. These mutations are present in at least half of familial cases of pulmonary arterial hypertension and 10 to 25% of idiopathic pulmonary arterial hypertension patients. Mutations in the gene that codes for activin receptor-like kinase (ALK 1), another transforming growth factor beta (TGF-beta) cell surface receptor, appear responsible for the rare occurrence of pulmonary arterial hypertension in patients with hereditary hemorrhagic telangiectasia. These discoveries coupled with other basic investigations offer opportunities for advances in the management of pulmonary arterial hypertension.
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PMID:Genetics of pulmonary arterial hypertension: current and future implications. 1612 12

Idiopathic pulmonary arterial hypertension (IPAH) is associated with proliferation of smooth muscle cells (SMCs) in small pulmonary arteries. Inhibition of proliferation of pulmonary artery smooth muscle cells (PASMCs) may be an effective treatment of patients with idiopathic pulmonary arterial hypertension. Recent studies have shown that carvedilol, an alpha- and beta-blocker with antioxidant and calcium channel blocking properties, inhibits the proliferation of cultured normal human pulmonary artery smooth muscle cells. In this study, we tested the hypothesis that carvedilol has antiproliferative effects on pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension. Pulmonary artery smooth muscle cells from six idiopathic pulmonary arterial hypertension patients who had undergone lung transplantation were cultured. To determine cell proliferation, H-thymidine incorporation was measured. Platelet-derived growth factor-induced proliferation of IPAH-PASMCs was significantly greater than that of normal control pulmonary artery smooth muscle cells. Carvedilol (0.1 microM to 10 microM) inhibited the proliferation of idiopathic pulmonary arterial hypertension-pulmonary artery smooth muscle cells in a concentration-dependent manner. Prazosin (an alpha-blocker) and N-acetyl L cysteine (an antioxidant agent) (0.1 microM to 10 microM) did not inhibit their proliferation, but the high concentration of propranolol (a beta-blocker) and nifedipine (a calcium channel blocker) (10 microM) inhibited the proliferation. The combination of propranolol and nifedipine inhibited the proliferation but only at a high concentration (10 microM) combination. Cell cycle analysis revealed that carvedilol (10 microM) significantly decreased the number of cells in S and G2/M phases. These results indicate that carvedilol inhibits the exaggerated proliferation of pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension partially via its beta-blocking [corrected] and calcium channel blocking effects in vitro.
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PMID:Carvedilol inhibits proliferation of cultured pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension. 1649 63

Idiopathic pulmonary arterial hypertension (IPAH) is characterised by in situ thrombosis and increased thromboxane (Tx) A2 synthesis; however, there are no studies of antiplatelet therapy in IPAH. The aim of the current study was to determine the biochemical effects of aspirin (ASA) and clopidogrel on platelet function and eicosanoid metabolism in patients with IPAH. A randomised, double-blind, placebo-controlled crossover study of ASA 81 mg once daily and clopidogrel 75 mg once daily was performed. Plasma P-selectin levels and aggregometry were measured after exposure to adenosine diphosphate, arachidonic acid and collagen. Serum levels of TxB2 and urinary metabolites of TxA2 and prostaglandin I2 (Tx-M and PGI-M, respectively) were assessed. A total of 19 IPAH patients were enrolled, of whom nine were being treated with continuous intravenous epoprostenol. ASA and clopidogrel significantly reduced platelet aggregation to arachidonic acid and adenosine diphosphate, respectively. ASA significantly decreased serum TxB2, urinary Tx-M levels and the Tx-M/PGI-M ratio, whereas clopidogrel had no effect on eicosanoid levels. Neither drug significantly lowered plasma P-selectin levels. Epoprostenol use did not affect the results. In conclusion, aspirin and clopidogrel inhibited platelet aggregation, and aspirin reduced thromboxane metabolite production without affecting prostaglandin I2 metabolite synthesis. Further clinical trials of aspirin in patients with idiopathic pulmonary arterial hypertension should be performed.
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PMID:A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension. 1650 59

Idiopathic pulmonary arterial hypertension is a disease involving small muscular pulmonary arteries and arterioles. Treatment with prostacyclin analogs and endothelin receptor antagonists is the cornerstone of therapy in these patients. Recent evidence suggests that phosphodiesterase-5 inhibitors such as sildenafil may improve functional capacity and hemodynamics in patients with pulmonary arterial hypertension. Despite these advances, pulmonary arterial hypertension remains a deadly and progressive disease and it has been suggested that combination therapy aimed at multiple targets may produce a greater improvement while minimizing adverse effects. We report three patients who declined after initial improvement on bosentan and subsequently showed an improvement in their functional capacity and brain natriuretic peptide (BNP) with the addition of sildenafil. This benefit has been sustained over a mean follow-up period of 19 (range 12-24) months.
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PMID:Long-term results after addition of sildenafil in idiopathic PAH patients on bosentan. 1692 86

Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease of unknown etiology. The exact pathogenesis of pulmonary arterial hypertension is still not well known. In the past decades, many protein molecules have been found to be involved in the development of IPAH. With proteomic techniques, profiling of human plasma proteome becomes more feasible in searching for disease-related markers. In present study, we showed the protein expression profiles of the serum of IPAH and healthy controls after depleting a few high-abundant proteins in serum. Thirteen spots had changed significantly in IPAH compared with healthy controls and were identified by LC-MS/MS. Alpha-1-antitrypsin and vitronectin were down-regulated in IPAH and may be valuable candidates for further explorations of their roles in the development of IPAH.
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PMID:Proteomic analysis of the serum in patients with idiopathic pulmonary arterial hypertension. 1744 95

Idiopathic pulmonary arterial hypertension (IPAH) is characterized by smooth muscle cell, endothelial cell, and fibroblast hypertrophy and an increase in extracellular matrix volume in pulmonary precapillary arterioles. These features lead to a gradual increase of pulmonary vascular resistance, right-heart failure, and premature death. Bone morphogenetic protein receptor type 2 (BMPR-2) gene mutations have been identified to cause IPAH. BMPR-2 receptor mutation results in BMP signalling pathway termination and leads to disturbed growth and differentiation of pulmonary circulation cells. Transforming growth factor (TGF)-beta1 inhibits the migration and proliferation of endothelial and smooth muscle cells, and stimulates their differentiation, thus it has antiinflammatory and immunosuppressive properties, inhibiting vascular remodeling and is responsible for extracellular matrix production. The aim of this study was to analyse the profile of TGF-beta1 and the expression of its receptor (TbetaR I, TbetaR II and TbetaR III-betaglycan) genes in IPAH and in secondary forms of pulmonary arterial hypertension [Eisenmenger's syndrome (ES) patients]. Twenty-one patients with IPAH (2 men), 12 ES patients, and 10 healthy controls were enrolled in the study. QRT-PCR analysis of the transcriptive activity of TGF-beta1 and its receptor genes was performed with each patient. There were differences in receptor gene expression among the patient groups. The highest expression was observed in Eisenmenger syndrome patients (approximately 5-to 8-fold increase). There was a negative correlation between the gene expression of TGF-beta1 and that of its receptors, and a positive correlation between TbetaR II and TbetaR III in healthy controls. In IPAH patients a positive correlation between TGF-beta1 and TbetaR I was found. There was a difference in expression of TGF-beta1/receptor gene ratios and expression of receptor gene ratios between the examined groups. The differences in expression between IPAH and ES patients might suggest the role of these cytokines in IPAH pathogenesis. A disturbed proportion of expression of TGF-beta1 and receptor genes in IPAH patients might be one of the pathogenetic factors of the disease.
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PMID:Expression of TGF-beta1 and its receptor genes (TbetaR I, TbetaR II, and TbetaR III-betaglycan) in peripheral blood leucocytes in patients with idiopathic pulmonary arterial hypertension and Eisenmenger's syndrome. 1809 22

Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disease characterised by elevated blood pressure in the pulmonary circulation. Initial vasoconstriction, proliferation of pulmonary arterial smooth muscle cells (PASMC) and increased deposition of extracellular matrix (ECM) contribute to pathological remodelling of pulmonary arterioles in IPAH. Glycosaminoglycans (GAGs), components of the ECM, control cellular proliferation and differentiation, but their expression in IPAH remains elusive. In the present study, GAG expression was investigated in the lungs of patients with IPAH or control transplant donors, and expression and localisation of GAG-metabolising enzymes were analysed in vivo and in vitro. A significant increase in the expression of hyaluronic acid (HA) was detected in IPAH lungs, associated with increased hyaluronan synthase (Has)1 and decreased hyaluronoglucosaminidase 1 gene expression, as assessed by quantitative RT-PCR and Western blotting. HAS1 protein localised to PASMC in vivo and increased HA deposition was observed in remodelled pulmonary arteries in IPAH. Transforming growth factor-beta1, a profibrotic growth factor, led to increased HA secretion and HAS1 expression in primary PASMC. The results demonstrate an increased hyaluronic acid content in idiopathic pulmonary arterial hypertension lungs, associated with increased hyaluronan synthase 1 and decreased hyaluronoglucosaminidase 1 gene expression. Synergistic regulation of glycosaminoglycan-metabolising enzymes in favour of accumulation may, thus, regulate pathological vascular remodelling in idiopathic pulmonary arterial hypertension lungs.
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PMID:Increased hyaluronic acid content in idiopathic pulmonary arterial hypertension. 1876 72

Idiopathic pulmonary arterial hypertension is a rare, but severe disease with high mortality. The endothelial dysfunction is a major pathogenesis of pulmonary arterial hypertension. Gene therapy, cell therapy and their combination therapy are developed to improve pulmonary hypertension by restoring the impaired endothelial function or regenerating endothelial cells. Although these therapies are still in experimental stage, they might be promising for pulmonary arterial hypertension. Here, we review the characteristics of the gene therapy, the cell therapy and the combination of them.
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PMID:[Gene therapy and cell therapy for idiopathic pulmonary arterial hypertension]. 1905 41


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