Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study evaluated the gastrointestinal absorption of fasudil, a novel Rho kinase inhibitor for the treatment of stable angina, at different sites using remote-controlled capsules and assessed the feasibility of developing an extended-release formulation. Ten healthy male volunteers were enrolled, and 8 subjects completed this single-dose, open-label, randomized, 5-way crossover study. Forty milligrams of fasudil HCl was administered as solution to the distal ileum and ascending colon, as powder to the ascending colon, and orally as an immediate-release tablet and solution. All treatments were well-tolerated and no serious adverse events were observed. The mean systemic availabilities of M3 relative to the oral solution were 1.04 (distal ileum, solution), 1.14 (ascending colon, solution), 1.27 (ascending colon, powder) and 1.04 (oral tablet), indicating similar systemic availability of M3 after administration of fasudil HCl to different gastrointestinal sites. The results suggest that development of a once-a-day extended-release formulation for fasudil HCl should be readily achievable.
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PMID:Systemic availability of the active metabolite hydroxy-fasudil after administration of fasudil to different sites of the human gastrointestinal tract. 1719 98

Rho protein represents a family of small GTP binding proteins that are involved in many important cellular functions including cell proliferation, migration and cytoskeletal reorganization. Rho protein is activated by GTP binding and is inactivated by hydrolyzing GTP to GDP. This process is influenced by variety of physiological and pathophysiological stimuli including growth factors, many vasoactive substances, smoking and mechanic stress or injury. Recent evidence suggest that targeting Rho protein per se or its downstream effector proteins such as Rho kinase or LIM kinase may have therapeutic potential in diseases such as hypertension, angina, myocardiac infarction (MI), atherosclerosis, tumor metastasis and spinal cord injury. Several recent patents have described modalities that regulate the activity of Rho, Rho kinase and LIM kinase as potential therapeutics. In this article, we will review the current knowledge on the cellular functions of Rho signaling pathway and strategies in targeting different components in Rho signaling pathway for human diseases with an emphasis on cardiovascular indications.
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PMID:Recent patents on Rho signaling pathway as therapeutic target for cardiovascular diseases. 1822 Oct 90

Objective. Hypoxia-induced sustained contraction of porcine coronary artery is endothelium-independent and mediated by PI3K/Akt/Rho kinase. Nitroglycerin (NTG) is a vasodilator used to treat angina pectoris and acute heart failure. The present study was to determine the role of NTG in hypoxia-induced endothelium-independent contraction and the underlying mechanism. Methods and Results. Organ chamber technique was used to measure the isometric vessel tension of isolated porcine coronary arteries. Protein levels of phosphorylated and total Akt were determined by western blot. A sustained contraction of porcine coronary arteries induced by hypoxia was significantly reduced by NTG but not by isoproterenol. This contraction was also inhibited by DETA NONOate, 8-Br-cGMP, which can be reversed by ODQ, and Rp-8-Br-PET-cGMPS. The restored contraction was blocked by LY294002. The reduction of Akt-p at Ser-473 by NTG, DETA NONOate, and 8-Br-cGMP was significantly inhibited by ODQ, PKG-I. The decrease in Akt-p level by NTG and 8-Br-cGMP was prevented by calyculin A but not by okadaic acid. Conclusions. These results demonstrated that the endothelium-independent sustained hypoxic vasoconstriction can be prevented by NTG and that the inhibition of PI3K/Akt signaling pathway may be involved.
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PMID:Endothelium-Independent Hypoxic Contraction Is Prevented Specifically by Nitroglycerin via Inhibition of Akt Kinase in Porcine Coronary Artery. 2683 58