Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to establish the possible existence of a cardiac converting enzyme and its role in the pathophysiology of the myocardial ischemia, the direct cardiac effects of IEC and AI or AII were studied on the isolated rat heart perfused through the left atria. Three series of seven hypertensive rats (SHR) were used. The reduction of the aortic flow (QAO) due to ischemia (produced by a left coronary artery ligation of 10 mn) was brought into line with the reduction of the coronary flow (QCORO) and the weight of the heart. This reduction was 2.06 +/- 1.8 for the control, 1.96 +/- 1.27 when captopril (CAP) (10(-5) M) was added to the perfusion liquid and 1 +/- 0.42 when perindopril (PER) (1.2 x 10(-5) M) was added to the perfusion liquid (p less than 0.05 vs CAP). Four series of 10 rat hearts (Sprague Dawley) were used to study the changes on the working heart caused by short perfusions of AI or AII (10(-7) M) in the presence of IEC or saralasin (SAR 10(-7) M). AII caused a reduction of the QCORO of 2.1 +/- 0.26 ml/mn, an increase of the QAO of 2.5 +/- 0.9 ml/mn and an increase of the heart rate (HR) of 9 +/- 3.24 beats/mn. In the presence of CAP or PER the effects of AII were the same, however in the presence of SAR these effects were prevented. AI caused a reduction of the QCOR of 2.5 +/- 0.4 ml/mn, an increase of the QAO of 2.5 +/- 0.8 ml/mn and an increase of the HR of 18 +/- 4 beats/mn.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Direct cardiac effects of angiotensins I and II and 2 converting enzyme inhibitors (captopril and perindopril). Indirect demonstration of a converting enzyme in the rat heart]. 284 75

The 1,3,4,5-tetrahydro-benzo[c][1,6]- and [c][1,7]-napthyridin-6-ones are presented as a potent class of PARP-1 inhibitors. Derivatives of these partially saturated aza-5[H]-phenanthridin-6-ones were designed and synthesized with tertiary amines for salt formation, thus enhancing aqueous solubility, iv formulation and their potential use in acute ischemic injuries (i.e., myocardial ischemia and stroke). We found that partial saturation of the C-ring results in derivatives that are several times more potent than the aromatic C-ring derivatives. The general synthetic routes are presented herein as well as thorough in vitro potencies and SAR discussion for selected derivatives.
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PMID:Design and synthesis of poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors. Part 3: In vitro evaluation of 1,3,4,5-tetrahydro-benzo[c][1,6]- and [c][1,7]-naphthyridin-6-ones. 1285 55

Rho kinase enzyme expressed in different disease conditions and involved in mediating vasoconstriction and vascular remodeling in the pathogenesis. There are two isoforms of Rho kinases, namely ROCK I and ROCK II, responsible for different physiological function due to difference in distribution, but almost similar in structure. The Rho kinase 2 belongs to AGC family and is widely distributed in brain, heart and muscles. It is responsible for contraction of vascular smooth muscles by calcium sensitization. Its defective and unwanted expression can lead to many medical conditions like multiple sclerosis, myocardial ischemia, inflammatory responses, etc. Many Rho kinase 1 and 2 inhibitors have been designed for Rho/Rho kinase pathway by use of molecular modeling studies. Most of the designed compounds have been modeled based on ROCK 1 enzyme. This article is focused on Rho kinase 2 inhibitors as there are many ways to improvise by use of Computer aided drug designing as very less quantum of research work carried out. Herein, the article highlights different stages of designing like docking, SAR and synthesis of ROCK inhibitors and recent advances. It also highlights future prospective to improve the activity.
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PMID:A review on ROCK-II inhibitors: From molecular modelling to synthesis. 2708 Jan 84