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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, endothelial dysfunction and arterial remodelling in various cardiovascular diseases have emerged as two key concepts, with numerous interrelationships. Both endothelial dysfunction and arterial remodelling occur in various pathologies including heart failure, atherosclerosis, restenosis after angioplasty, and pulmonary hypertension, and have modified the therapeutic approach by offering new pharmacological targets: specific receptors not only at the site of the vascular smooth muscle cells but also on the endothelial cells, growth factors that stimulate proliferation of smooth muscle, and receptors and enzymes of the extracellular matrix. Among the various substances under research, the present review will discuss angiotensin II receptor antagonists, endothelin receptor antagonists, nitrates-NO donors, potassium channel activators, and substances interfering with proteoglycans and other components of the extracellular matrix.
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PMID:[Arterial wall: a new pharmacological and therapeutic target?]. 748 94

To investigate the mechanism by which angiotensin-converting enzyme (ACE) inhibition attenuates atherogenesis, we have studied the effects of a non-sulfhydryl ACE inhibitor, enalapril, and an angiotensin receptor antagonist, SC-51316, in cholesterol-fed rabbits. After 3 mo of enalapril treatment (10 mg/kg per d, p.o.) the percent plaque areas in the thoracic aortas of treated animals were significantly reduced (controls: 86.8 +/- 3.5%; treated: 31.1 +/- 8%, P < 0.001). Aortic cholesterol content was also reduced (controls: 31.4 +/- 3.2 mg/g tissue; treated: 7.4 +/- 1.8 mg/g, P < 0.001). Enalapril had no significant effect on plasma lipid levels or conscious blood pressure. In a second study, the angiotensin II receptor antagonist SC-51316 was administered at a dose equivalent to enalapril at blocking angiotensin pressor effects in vivo (30 mg/kg per d, p.o.). Evaluation after 3 mo indicated no significant attenuation of aortic atherosclerosis. These results demonstrate that: (a) enalapril attenuates atherogenesis without affecting either blood pressure or plasma lipid levels; (b) antioxidant activity, found with sulfhydryl-containing ACE inhibitors, is not necessary for reducing plaque formation; and (c) the attenuation of atherogenesis by ACE inhibition may not be due to blockade of the renin-angiotensin system. Alternatively, one must consider the multiple effects of ACE inhibition on other hormone systems, such as bradykinin, or the possibility that alternate angiotensin II receptors may be involved in atherosclerosis.
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PMID:Differential effects of renin-angiotensin system blockade on atherogenesis in cholesterol-fed rabbits. 847 94

Chronic renal allograft dysfunction is often associated with hypertension, but it is unknown to what extent this affects graft structure and function. We investigated the effect of antihypertensive drug treatments on the course and histopathology of chronic renal allograft rejection in a rat model. Recipient animals were treated with a combination of reserpine, hydralazine and hydrochlorothiazide, the angiotensin converting enzyme inhibitor cilazapril, or the angiotensin II receptor blocker L158,809. Systemic blood pressures and tubular stop-flow pressures were measured on day 50 after transplantation; the histopathology was assessed semiquantitatively in kidneys not used for micropuncture studies. Grafts removed from untreated recipients showed inflammation and structural vascular and glomerular lesions consistent with chronic rejection. All treatment regimens decreased the systemic and glomerular capillary pressures and were associated with improved graft survival, decreased proteinuria and a tendency to improved graft function; the histopathology showed a significant amelioration of glomerular mesangiolysis and glomerulosclerosis but no effect was found on the tubulointerstitial lesions; the angiotensin receptor blocker also inhibited graft atherosclerosis. We conclude that hemodynamic and angiotensin II-mediated processes may play a pivotal role in the expression of immune-mediated glomerular lesions of chronic allograft dysfunction.
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PMID:Post-transplant hypertension and chronic renal allograft failure. 858 80

In recent years, two key concepts having numerous interrelationships were advanced for the understanding of various cardiovascular diseases: the "endothelial dysfunction" and the "arterial remodelling". Both endothelial dysfunction and arterial remodelling occur in various pathologies including essential hypertension, heart failure, atherosclerosis, restenosis after angioplasty, and pulmonary hypertension, and have modified the therapeutic approach by offering new pharmacological targets: specific receptors not only at the site of the vascular smooth muscle cells but also on the endothelial cells, growth factors that stimulate proliferation of smooth muscle, and receptors and enzymes of the extra-cellular matrix. Among the various substances under research, the present review will discuss angiotensin II receptor antagonists, endothelin receptor antagonists, nitrates-NO donors, potassium channel activators, and substances interfering with proteoglycans and other components of the extra-cellular matrix.
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PMID:The arterial wall: a new pharmacological and therapeutic target. 883 98

Genetic variations in the renin-angiotensin and kallikrein-kinin systems could prove to be significant pathophysiological mechanisms affecting coronary heart disease (CHD), particularly given the powerful vasoactivity of products such as angiotensin II and bradykinin. Indeed, studies show that angiotensin converting enzyme (ACE) gene polymorphism is associated with an increased risk of myocardial infarction and death, even in otherwise low-risk subjects. Genetic differences do not appear to be a risk factor for atherosclerosis or hypertension, however. Because ACE polymorphism modulates local production of angiotensin II, a powerful coronary vasoconstrictor, it may influence left ventricular mass in general as well as in coexisting disease states such as hypertension and cardiomyopathy. However, further study is needed to clarify the implications of ACE polymorphism in patients with left ventricular hypertrophy. Interactions between ACE and angiotensin II type-1 receptors may have clinical implications for preventing and managing CHD. Screening for genetic risk, as evidenced by certain variants in receptor coding sequence, may prove worthwhile if detrimental effects can be countered by drugs such as ACE inhibitors and angiotensin II receptor blockers. Given the important roles of angiotensin II and bradykinin as modulators of cellular growth and of vasoactivity, deleterious and beneficial effect at different stages of the atherosclerotic process and during acute events leading to myocardial infarction or sudden death can be suspected.
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PMID:Angiotensin I converting enzyme gene polymorphism and coronary heart disease. 886 31

To gain insight into the contribution of immunologic and hemodynamic factors in the progressive demise of structure and function in chronic renal allograft dysfunction, we studied the histological changes, the immunostainable glomerular anionic sites, and glomerular capillary hydrostatic pressures of rat renal allografts with chronic rejection. Recipient animals were left untreated, received 8 weeks of treatment with the immunosuppressive drug cyclosporine, or received antihypertensive drugs consisting of the combination of reserpine, hydralazine and hydrochlorothiazide, the angiotensin-converting enzyme inhibitor cilazapril, or the angiotensin II receptor blocker L-158,809. Grafts in untreated recipients developed chronic interstitial inflammation, as well as vascular and glomerular lesions consistent with chronic rejection. These lesions were associated with immunohistochemical loss of the negatively charged heparan sulfate proteoglycan side chain. All treatment regimens decreased the systemic and glomerular capillary pressures and were associated with no loss of function, decreased proteinuria, and a tendency to improved graft function. Cyclosporine prevented all histological manifestations of rejection, and antihypertensive drugs decreased the extent of glomerular mesangiolysis and glomerulosclerosis; L-158,809 and cilazapril also inhibited graft atherosclerosis and tubular atrophy. We conclude that chronic rejection is primarily an immune-mediated process, but hemodynamic and angiotensin II-mediated effects may play a pivotal role in the expression of immune-mediated lesions.
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PMID:Antihypertensive drug treatment in chronic renal allograft rejection in the rat. Effect on structure and function. 897 Jun 20

To investigate how the renin-angiotensin system (RAS) might be involved in cholesterol-induced atherosclerosis, we studied the effects of a nonsulhydryl angiotensin converting enzyme (ACE) inhibitor, enalapril, and an angiotensin II receptor antagonist, E-4177, in cholesterol fed rabbits. Japanese white rabbits were randomly divided into four groups with the following dietary regimens: group A (n = 8) received a standard diet; group B (n = 8) had a 0.5% cholesterol diet; group C (n = 8) had a 0.5% cholesterol diet plus enalapril (10 mg/kg/day, p.o.); group D (n = 8) received a 0.5% cholesterol diet plus E-4177 (20 mg/kg/day, p.o.) and were fed these diets for 5 weeks. Enalapril or E-4177 had no significant effect on either the total plasma or the high density lipoprotein (HDL) cholesterol concentrations. However, the aortic cholesterol content in groups C and D was equally significantly less than that in group B. The plasma and aortic ACE activities were significantly reduced only in group C compared with those in the other groups. The aortic ACE mRNA and AT1 mRNA levels were assessed by a reverse transcription polymerase chain reaction (RT-PCR). The aortic ACE mRNA level was only significantly less in group C than in any of the other groups. The aortic AT1 mRNA level increased significantly in group B compared with that in group A and was significantly and equally reduced in both groups C and D compared with that in group B. These data indicate that angiotensin II rather than ACE may therefore be related to aortic cholesterol content. It follows therefore that the inhibition of angiotensin II by either ACE inhibitor or angiotensin II (type 1) receptor antagonist may play a role in prevention of atherosclerosis.
Atherosclerosis 1996 Nov 15
PMID:The effects of renin-angiotensin system inhibition on aortic cholesterol content in cholesterol-fed rabbits. 900 12

ACE inhibitors have been shown to be effective in reducing the morbidity and mortality of patients with left ventricular systolic dysfunction, but their application to clinical practice in this situation is still limited. In part, the failure to prescribe an ACE inhibitor to a patient with left ventricular systolic dysfunction is due to perceptions regarding their side effects, such as cough and renal dysfunction. Relatively few patients with left ventricular systolic dysfunction and a serum creatinine > or = 2 mg/dl receive an ACE inhibitor in clinical practice. In this situation one should consider an agent such as fosinopril, which is metabolized by the liver as well as secreted by the kidney. In patients with moderate renal dysfunction, fosinopril has been well tolerated without an increase in serum creatinine. In patients who develop cough due to an ACE inhibitor, consideration should be given to an angiotensin II type 1 receptor blocking agent, such as losartan. The relative safety and efficacy of an ACE inhibitor compared with an angiotensin II type 1 receptor blocking agent is being explored in a prospective randomized trial (Evaluation of Losartan In The Elderly [ELITE]), as well as the safety and pharmacological effectiveness of adding an angiotensin II receptor antagonist to an ACE inhibitor (Randomized Angiotensin receptor antagonists-ACE-inhibitor Study [RAAS]). There may also be a role for the combination of an aldosterone receptor antagonists and an ACE inhibitor in patients with left ventricular systolic dysfunction. Once an ACE inhibitor is administered to a patient with left ventricular systolic dysfunction it should be continued indefinitely. ACE inhibitors may be of value not only in preventing the progression of heart failure but also in reversing endothelial dysfunction and preventing the development of atherosclerosis and its consequences, such as myocardial infarction.
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PMID:ACE inhibitors in heart failure: prospects and limitations. 921 Oct 22

Renovascular hypertension is a potentially curable, secondary form of hypertension. It is caused by renal ischemic disease, which remains a significant clinical problem because of the increasing incidence of atherosclerosis with aging of the overall population. The role of the reinin-angiotensin system in renovascular hypertension has been consolidated by the discovery of angiotensin II receptor subtypes, various tissue renin-angiotensin systems and the function of angiotensin II as a vascular growth factor. To date renal vein renin estimation and converting enzyme renography seem to be the most reliable investigations to demonstrate the hypertensive role of a kidney before revascularization. Percutaneous transluminal angioplasty is a successful treatment in selected forms of renal artery stenosis. Open surgery consists of either bypass procedure or renal autotransplantation with extracorporeal reconstruction of the renal vasculature in cases of aneurysms or segmental renal artery stenoses. Control of hypertension and, increasingly important, preservation of renal function can be safely and successfully achieved, on the basis of careful diagnosis and individual selection of the therapeutic procedure are performed.
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PMID:[Renovascular arterial hypertension: current aspects of physiopathology, diagnosis and treatment]. 924 50

The potential antiatherogenic actions of the angiotensin II receptor antagonist, losartan were investigated in apolipoprotein (apo) E deficient mice, an animal model with severe hypercholesterolemia and extensive atherosclerosis. In these animals accelerated atherosclerosis is associated with increased lipid peroxidation which may play a crucial role in the build up of the atherosclerotic lesions. Administration of losartan (25mg/kg/d) to the apo E deficient mice for a 3-month period increased the plasma renin activity 3.5-fold compared to the placebo group. Losartan increased the resistance of LDL to CuSO4-induced oxidative modification as shown by a significant reduction in the LDL content of malondialdehyde by 55% compared to placebo, as well as by the prolongation of the lag time required for LDL oxidation, from 60 min in the placebo-treated mice to more than 140 min in the losartan-treated mice. Losartan reduced significantly the mean atherosclerotic lesion area by 80% compared to the placebo group. We conclude that losartan inhibits LDL lipid peroxidation in the apo E deficient mice and this effect may have an important role in the attenuation of the accelerated atherosclerosis.
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PMID:The angiotensin-II receptor antagonist, losartan, inhibits LDL lipid peroxidation and atherosclerosis in apolipoprotein E-deficient mice. 924


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