Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4), a novel angiotensin I converting enzyme inhibitor, on cardiovascular, visceral and renal functions and on hemodynamics, were studied in various experimental animals. Even at a high dose of 100 mg/kg p.o. benazepirl hydrochloride had no influence on the respiration, heart rate and ECG of normotensive anesthetized cats and, except at higher doses, had little effect on the contractile tension of mammalian isolated atrium, ileum, trachea, stomach fundus strips, vas deferens or uterus. Benazepril hydrochloride even at a high dose of 100 mg/kg p.o. had little effect on spontaneous uterine motility, charcoal transportation and gastrointestinal tract motility. In addition, it did not cause gastric irritation, alter the secretion of gastric and biliary juices, and did not affect the tension of the nictitating membrane or the twitch tension of the gastrocnemius muscle in various experimental animals. Benazepril hydrochloride had no effect on the blood glucose and cholesterol levels in alloxan-induced diabetic rats but decreased the triglyceride and total cholesterol levels in normotensive rats at a dose of 30 mg/kg p.o. Benazepril hydrochloride at 3 mg/kg.day s.c. for 10 weeks caused a significant decrease in aortic atherosclerosis without reducing hypercholesterolemia in cholesterol-fed rabbits. Benazepril hydrochloride at a high dose of 100 mg/kg p.o. showed no effect on the urine volume and urinary excretion of electrolytes but decreased PSP excretion in normotensive rats. At a dose of 3 or 10 mg/kg.day p.o. for 4 weeks benazepril hydrochloride inhibited the increase in the excretion of urinary protein in DOCA/salt spontaneously hypertensive rats. It caused hemolysis at concentrations as high as 0.1-1% in rabbits, however, even at a high dose of 100 mg/kg p.o. it did not affect red blood cell fragility in rats, and, except at a high dose of 10(-4) g/ml, showed little effect on the platelet aggregation response induced by collagen or arachidonic acid in rabbits. From these results, benazepril hydrochloride is considered to be a safe and well-tolerated addition to the therapeutic armamentarium of cardiovascular drugs.
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PMID:General pharmacology of the novel angiotensin converting enzyme inhibitor benazepril hydrochloride. Effects on cardiovascular, visceral and renal functions and on hemodynamics. 179 19

It is well established that cardiac dysfunction independent of atherosclerosis develops in both humans and animals with diabetes mellitus. The etiology is complex, involving many different processes, one of which may be increased fatty acid utilization and/or a concomitant decrease in glucose utilization by the diabetic heart. We compared control and 6-wk streptozotocin (STZ)-induced diabetic isolated working rat hearts and were able to demonstrate cardiac dysfunction in the diabetic as assessed by depressed heart rate (HR), heart rate peak systolic pressure product (HR.PSP), left ventricular developed pressure (LVDP), and rate of pressure rise (+dP/dt). Paralleling depressed cardiac function in the diabetic were hyperglycemia, hyperlipidemia, and decreased body weight gain compared with age-matched controls. The addition of free fatty acids, in the form of 1.2 mM palmitate, to the isolated working heart perfusate had no effect on either control or diabetic heart function, with the exception of a depressive effect on +dP/dt of diabetic hearts. But diabetic hearts perfused with palmitate-containing perfusate plus the glucose oxidation stimulator dichloroacetate (DCA) showed a marked improvement in function. HR and HR.PSP in spontaneously beating hearts, as well as LVDP and +dP/dt in paced hearts were all restored to control heart values in diabetic hearts perfused in the presence of DCA. Creatine phosphate and ATP levels were similar under all perfusion conditions, thus eliminating energy stores as the limiting factor in heart function. Results indicate that DCA will acutely reverse diabetic cardiac function depression. Therefore glucose oxidation depression in the diabetic heart may be a significant factor contributing to cardiac dysfunction.
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PMID:Effects of free fatty acids and dichloroacetate on isolated working diabetic rat heart. 192 88

Macrophage-derived foam cells and platelets are found in many lesions of atherosclerosis. Macrophages possess scavenger receptors that take up modified low density lipoproteins (LDL) like acetylated or acetoacetylated LDL (aLDL, aaLDL) resulting in accumulation of esterified cholesterol (EC) and acquisition of the characteristics of foam cells. We obtained a certain platelet secretory product from washed platelet-rich plasma which had been frozen and thawed three times (PSP alpha). We studied the effect of PSP alpha in modified lipoprotein metabolism in macrophages. When mouse or human macrophages were incubated with aaLDL and PSP alpha, much more EC was accumulated than with aaLDL only. Though the increase in EC of macrophages was dependent on the concentration of PSP alpha, it declined in high concentrations of PSP alpha. PSP alpha moderately increased 125I-aaLDL binding and cellular metabolism. PSP alpha also affected 125I-oxidized LDL binding and cellular metabolism, but it did not affect the metabolism of 125I beta-migrating very low density lipoprotein (beta VLDL). These results suggest that substances shed by activated platelets play a role in atherosclerosis as potent mediators of EC accumulation in macrophages and by affecting the receptor-mediated endocytosis of modified lipoproteins.
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PMID:Role of platelet secretory products in modified lipoprotein metabolism in macrophages. 276 30

The present report concerns the demonstration and distribution of tau-positive structures in the frontal and temporal white matter of five autopsy cases of early onset Alzheimer's disease (AD). The relationship between white matter lesions and tau positive structures was also investigated. Five early onset AD brains, which had not only unambiguous white matter lesions, but also no or rare atherosclerosis and minimal amyloid angiopathy, were examined. There were several tau-positive coiled body-like structures and many thread-like structures in the white matter, although previous reports showed only a few coiled bodies in the white matter in the AD brain. No relationship was found between the degree of each white matter lesion and number or distribution of tau-positive structures in the white matter. The results suggest that the AD brain has tau-positive structures in the white matter similar to some neurodegenarative brain diseases such as progressive supranuclear palsy, corticobasal degeneration, and dementia with grains. However, tau abnormalities may have fewer effects when they are located in white matter lesions in AD.
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PMID:Demonstration and distribution of tau-positive glial coiled body-like structures in white matter and white matter threads in early onset Alzheimer's disease. 1203 Apr 17