TY -的T1 -ρ为肺激酶抑制剂hypertension: waiting for clinical evidence JF - European Respiratory Journal JO - Eur Respir J SP - 709 LP - 711 DO - 10.1183/09031936.00100410 VL - 36 IS - 4 AU - Pacaud, P. AU - Loirand, G. Y1 - 2010/10/01 UR - //www.qdcxjkg.com/content/36/4/709.abstract N2 - Pulmonary arterial hypertension (PAH) is a rare disease characterised by a progressive increase of pulmonary vascular resistance (PVR) and pulmonary arterial pressure (Ppa), leading to right ventricle hypertrophy and death 1, 2. Although major advances in the understanding of disease development and treatment have been achieved over the past two decades, the pathogenesis of PAH is still not clearly understood. Idiopathic, familial and connective tissue disease-associated forms of PAH display similar pathological changes and are considered to share common pathogenic mechanisms, which involve endothelial dysfunction, endothelial and smooth muscle cell proliferation, increased vasoconstriction and in situ thrombosis 2. The consequence of this process is right ventricular ischaemia, remodelling, dilation, dysfunction and failure 3. Accordingly, current therapies are based on the use of drugs that improve endothelial function. Pharmacological agents targeting the endothelin (ET)-1 (ET-1 receptor antagonists, such as bosentan or sitaxentan), the nitric oxide (sildenafil, type 5 phosphodiesterase inhibitor), or the prostacyclin (epoprostenol, iloprost) pathways have shown benefits for patients with PAH 4. However, these treatments failed to improve the long-term survival and their use is hampered by either side-effects or inconvenient drug administration routes 5. Indeed, none of the currently available therapies is curative, so the search for new targets for novel therapeutic strategies continues.Among promising targets recently identified is the serine-threonine kinase Rho kinase. Two isoforms of Rho kinase, Rock-1 and Rock-2, have been identified and found to be expressed in arteries. Rho kinase regulates a variety of cellular functions including motility, proliferation, apoptosis, contraction and gene expression 6. Rho kinase is considered to be a major determinant of arterial tone, through its essential role in the regulation of the Ca2+ sensitivity of smooth muscle cell contraction. Furthermore, Rho kinase negatively controls endothelial nitric oxide synthase expression and … ER -