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)

Pre-eclampsia is suggested to be characterized by a functional imbalance between vascular prostacyclin and thromboxane A2 production. On the basis of this hypothesis it is attempted to correct this pathologic conditions by pharmacological manipulation with Trapidil, a triazolo pyrimidin derivative, because of its effects on the prostanoid metabolism. A prospective, randomized, double blind, placebo-controlled study was carried out to investigate Trapidil in the prevention of pregnancy-induced hypertension or pre-eclampsia. A total of 160 pregnant women with the risk to develop pre-eclampsia received Trapidil or placebo between week 24 and 38 of gestation. The number of patients in whom pregnancy-induced hypertension or pre-eclampsia developed was significantly lower in the Trapidil-treated (5.5%) compared with the placebo-treated group (14.1%). Additionally, a reduced risk of preterm deliveries and severe fetal growth retardation could be observed. In 7 patients with manifest pre-eclampsia or pregnancy-induced hypertension the circulating eicosanoid concentrations were determined before and during Trapidil medication. Trapidil was associated with an about twofold increase of 6-keto PGF1 alpha concentration in the peripheral venous blood, while the concentration of thromboxane A2 revealed no changes.
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PMID:[Effect of trapidil in prevention of pre-eclampsia and fetal retardation]. 787 57

Trapidil, an antiplatelet drug, has been shown to reduce restenosis after angioplasty. It exerts its action, at least in part, by inhibiting vascular smooth muscle cell proliferation, antagonizing platelet-derived growth factor (PDGF). We examined its site of action on PDGF cellular signaling. Exposure of cultured rat vascular smooth muscle cells to increasing concentrations of trapidil for 18 hours resulted in a dose-dependent reduction in PDGF-BB-stimulated [3H] thymidine incorporation. Trapidil (400 microg/mL) increased PDGF beta-receptor protein by 28+/-8%, whereas PDGF-induced tyrosine phosphorylation of PDGF beta-receptor remained unchanged. PDGF-induced tyrosine phosphorylation of phospholipase Cgamma, the p85 regulatory subunit of phosphatidyl-inositol 3 kinase, Ras GTPase-activating protein, and an adaptor molecule Shc were also not altered. On the other hand, trapidil inhibited PDGF-stimulated mitogen-activated protein kinase (MAP kinase) activity by 35+/-7% at 10 minutes and by 32+/-10% at 6 hours. Activation of Raf-1, an upstream activator of MAP kinase, by PDGF was also attenuated by trapidil. Moreover, protein content of MAP kinase phosphatase-1, which inactivates MAP kinase, was elevated in trapidil-treated cells. These actions of trapidil may be mediated by cAMP. Thus, there was a 1.9-fold increase in cellular cAMP generation in trapidil-treated cells. The present results demonstrate that trapidil antagonizes PDGF-induced mitogenesis and MAP kinase activation in vascular smooth muscle cells, probably through cAMP.
Hypertension 1998 Feb
PMID:Trapidil inhibits platelet-derived growth factor-stimulated mitogen-activated protein kinase cascade. 946 Dec 38

The increase in thickening of the arterial wall of pulmonary arterial hypertension (PAH) includes cellular proliferation as well as matrix deposition and interrupted internal elastic lamina (IEL) consisting of a thick homogeneous sheet of elastin. Little is, although, known about the detail of IEL formation in PAH. Endothelin-1 is overexpressed in pulmonary arterioles of PAH. We aimed to examine the expression of genes contributing to IEL formation in pulmonary artery smooth muscle cells (PASMCs) especially focused on lysyl oxidase (LOx), an exreacellular matrix enzyme that catalyzes the cross-linking of collagens or elastin. We quantified mRNA expressions of genes contributing to IEL formation including LOx in PASMCs using real-time quantitative polymerase chain reaction. We stimulated human PASMCs with endothelin-1 with prostacyclin or trapidil. Endothelin-1 significantly increased LOx expression. Prostacyclin and trapidil restored endothelin-1-induced LOx expression to the basal level. Endothelin-1 increased LOx expression strongly in PASMCs from PAH patients compared to those from controls. Trapidil reduced LOx expression only in PASMCs from PAH patients. Overexpressed endothelin-1 in PAH patients can increase expression of LOx and agitate cross-linking of elastin and collagen, resulting in ectopic deposition of these in the vascular media.
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PMID:Endothelin-1 induces lysyl oxidase expression in pulmonary artery smooth muscle cells. 3261 41