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)

Typical causes of renovascular hypertension include intramural atherosclerotic lesions of the main renal arteries or their branches and fibromuscular dysplasia of the renal arterial wall with luminal narrowing. We report a patient with new-onset, accelerated hypertension (blood pressure 220/140 mm Hg, status epilepticus, retinal hemorrhages) secondary to a dissection of the anterior division of the right renal artery that was accompanied by hyperreninemia, hyperaldosteronism, and hypokalemia. At presentation in the untreated state, unstimulated plasma renin activity and the serum aldosterone level were markedly elevated. Following right nephrectomy, blood pressure levels normalized without antihypertensive therapy, and plasma renin activity, serum aldosterone and potassium levels normalized. Histologic study of the right renal artery showed an isolated dissection of the anterior branch of the vessel between the muscularis and adventitia that created marked reduction in luminal diameter and renal ischemia. There was no evidence of any other vascular abnormalities, atherosclerosis, or fibromuscular dysplasia. These findings demonstrate that an isolated dissection of a branch of the renal artery may induce profound hyperreninemia and represents a rare, reversible etiology for accelerated hypertension associated with acute encephalopathy.
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PMID:Accelerated hypertension with encephalopathy due to an isolated dissection of a renal artery branch vessel. 820 71

Based upon literature the renin-angiotensin system involvement in the pathogenesis of atherosclerosis has been discussed. Angiotensin II leads to the increased production of growth factors such as PDGF, TGF-beta, FGF and extracellular matrix proteins. There are evidences that angiotensin II stimulates expression of egr-1, c-jun, c-fos and c-myc oncogenes in vascular smooth muscle cells. Proliferation of aortic smooth muscle cells in response to the injury can be reduced by inhibitors of renin-angiotensin system what supports the hypothesis that angiotensin II can contribute to the pathogenesis of atherosclerosis.
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PMID:[Renin-angiotensin system and atherosclerosis]. 820 30

Antihypertensive treatment in the diabetic patient is a critical issue because hypertension has an impact on all of the vascular complications of diabetes, including nephropathy, retinopathy, atherosclerosis, and left ventricular hypertrophy. These complications are a consequence of altered endothelial-vascular smooth muscle interrelations that ultimately enhance vasoconstriction and alter the remodeling processes in the vascular wall. Several observations suggest that the renin-angiotensin system (RAS) may be an important contributor to these processes in diabetes mellitus. In both animal and human studies, angiotensin-converting enzyme (ACE) inhibitors have been demonstrated to slow the progression of glomerulosclerosis, prevent abnormal remodeling processes in the heart following injury, and slow the progression of atherosclerosis. In particular, ACE inhibitors appear to protect the kidney more than would be expected from simply the lowering of blood pressure and decreasing of intraglomerular pressure, possibly because angiotensin II has both hemodynamic and direct effects on the glomerulus. Paradoxically, however, the activity of the circulating RAS is low in diabetic patients. Part of these seemingly inconsistent observations may be due to (1) potential activity of tissue RASs, (2) increased sensitivity to angiotensin II in diabetes, or (3) an effect of ACE inhibition on other systems in addition to the RAS. Investigation of these mechanisms will be important in determining the therapeutic role of inhibition of the RAS in diabetes mellitus.
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PMID:Systemic hypertension and the renin-angiotensin system in diabetic vascular complications. 828 77

For more than a decade, the inhibition of the renin-angiotensin system in heart failure has been regarded as pure vasodilator therapy. Consequently, the role of the renin-angiotension system has been seen as contributing to hemodynamic overload by vasoconstriction and volume retention. Meanwhile, clinical experience was indicated that important additional aspects of ACE-inhibition in heart failure are attenuation of the enhanced neuroendocrine activity and reversal or prevention of inappropriate trophic reactions of the overloaded myocardium. In overloaded hearts there is enhanced intracardiac formation of angiotensin due to enhanced expression of angiotensinogen and ACE, and due to accumulation of circulating, nephrogenic active renin. In human hearts, a mast-cell-derived chymase, which is not blocked by ACE-inhibition, contributes to intracardiac angiotensin formation. The enhanced intracardiac angiotensin-II formation in overloaded hearts is involved in coronary constriction, impairment of diastolic relaxation, myocyte enlargement and interstitial fibrosis, which aggravate the diastolic impairment. The major problem in overloaded, hypertrophied cardiocytes is the dedifferentiation with instabilization of Ca(++)-homeostasis due to an altered program of gene expression. Dedifferentiated cardiocytes have a reduced expression of sarcoplasmic reticulum Ca(++)-ATPase and an enhanced expression of the sarcolemmal Na+/Ca(++)-exchanger, resulting in an attenuation of active diastole (Ca(++)-reaccumulation into the sarcoplasmic reticulum), a depressed force-frequency relation, and an enhanced susceptibility for fatal arrhythmias. Furthermore, an enhanced local renin-angiotensin system in distensible coronary and systemic arteries seems to contribute to a reduced releasability of endothelium-derived relaxing factor, probably by reducing bradykinin availability. This modulation of endothelial function appears to contribute to the localization and progression of atheroma development in presence of risks factors for atherosclerosis.
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PMID:Pathophysiology of heart failure and the renin-angiotensin-system. 835 33

While the circulating renin-angiotensin system (RAS) plays an important role in short-term maintenance of cardiovascular homeostasis, recent studies point to a role in long-term cardiovascular regulation for endogenous RAS in target tissues. This article focuses on the multiple effects of tissue angiotensin enzyme (ACE) and angiotensin II (Ang II), its active peptide product. Ang II has been shown to be a potent growth factor in vascular smooth muscle cells. Depending on the local conditions, the vascular response may be either hypertrophy or hyperplasia. The molecular mechanisms involved in the interactions of Ang II with endothelium- and smooth muscle-derived cell products may play important roles in the modulation of vascular structure in hypertension and vascular injury. Evidence also points to a role for Ang II in the development of left ventricular hypertrophy in hypertension. In addition, cardiac RAS may contribute to the pathophysiology of heart failure. Experimental and clinical studies with ACE inhibitors point to a role for tissue ACE activity in the development of atherosclerosis, as well as cardiac hypertrophy and remodeling.
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PMID:Local expression and pathophysiological role of renin-angiotensin in the blood vessels and heart. 839 69

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

The role of renin-angiotensin system in the development of atherosclerosis is not yet defined, even though several actions of angiotensin II have been suggested as contributing to the development of the atherosclerotic lesion. Local renin-angiotensin system may exert a variety of autocrine or paracrine influences on vascular tissue leading to important trophic and growth regulatory effects and participating to well known events in atherogenesis as control of smooth muscle cell growth and proliferation. The existence and the specific function of components of this system in blood vessels wall suggest its possible involvement in atherosclerotic process. On these bases, the antiatherogenic properties of ACE-inhibitors have been recently evaluated in animal models where a protective effect of ACE-inhibition over the development of experimental atherosclerotic lesions has been observed. This favorable effect could follow the antihypertensive action of ACE-inhibitors even whether other potential mechanisms, including prevention of angiotensin II-induced vascular proliferation and interference with sympathetic nervous system activity and insulin sensitivity, have to be considered. Despite some clear-cut experimental evidences, the clinical importance of such findings as well as the precise mechanisms by which ACE-inhibition is able to interfere with the pathogenesis of atherosclerosis is still matter of debate and need to be assessed in future investigations.
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PMID:Ace-inhibitors and experimental atherosclerosis. 851 7

Many cell types in myocardial tissue, including cardiocytes, contain receptors for angiotensin-II, but the activation of these receptors requires angiotensin concentrations in the micromolar range, which do not occur in plasma in vivo. However, angiotensins formed locally in the heart can activate these receptors in a paracrine and autocrine mode. In cardiac hypertrophy due to hemodynamic overload, the myocardial angiotensin formation is enhanced due to an augmented expression of angiotensinogen and ACE. Though the mRNA for prorenin is expressed in myocardium, the formation of active renin within the heart has not yet been demonstrated and myocardial renin activity is mainly due to contamination from circulating active renin. Intracoronary application of ACE inhibitors in hypertrophied hearts in vivo and in vitro indicates that the locally formed angiotensin-II contributes to coronary constriction, impairment of diastolic relaxation and marginally to the maintenance of systolic tension development. Angiotensin-II can exert trophic effects on cardiocytes and cardiac fibroblasts, and chronic inhibition of the cardiac RAS by ACE-inhibitors or AT receptor antagonists can induce partial regression of overload hypertrophy, even without normalizing the overload. This anti-trophic action may be partially due to the impairment of the angiotensin axis, but also due to enhancement of bradykinin availability, which results in an augmented release of endothelial anti-trophic signals such as EDRF/NO and prostacyclin. Preliminary evidence is compatible with the hypothesis that an activated local RAS in elastic arteries contributes to the localization and progression of atherosclerosis by suppressing EDRF releasability. However, the anti-atherosclerotic potential of ACE inhibitors and AT receptor antagonists in humans is still unknown.
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PMID:The cardiac renin-angiotensin system: physiological relevance and pharmacological modulation. 851 37

Independently of phenomena related to rejection, atherosclerosis of the grafted heart or high blood pressure, there exists a qualitative and quantitative degradation of response to exercise in heart transplant recipients. Maximal oxygen consumption is generally reduced to 40 to 60% of normal levels. There are several interactive mechanisms. Paradoxically, the transplanted heart is a clear demonstration of the fact that several other elements are involved in the organisms response to exercise. Indeed, ventilation, exercise load, peripheral circulation, muscle metabolism and neurohormonal response also play a role. Vasoactivity of the peripheral arteries limits distribution and extraction of oxygen during exercise. Noradrenaline, renin, atrial natriuretic factor, vasopressin and endothelin levels are normal at rest, but an overreaction occurs during exercise. The percentage of type I (oxidative) fibres is reduced in muscles. Cyclosporine has also been shown to have a toxic effect on mitochondria in muscles. The deinnervated transplanted heart is thus called upon to work in coordination with peripheral elements which have also undergone alterations. Consequently, response to exercise cannot be significantly increased above the level reached before transplantation. Usually patients are not greatly hindered in their daily activities and rarely complain of breathlessness. Nevertheless, an improvement would be appreciated. A coherent physical rehabilitation programme can increase maximal oxygen consumption by 25 to 30% in these patients, essentially via improvement in peripheral anomalies. It is more difficult to modify cardiac response.
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PMID:[Exercise capacity after heart transplantation]. 854 31

Angiotensin converting enzyme inhibitors (CEI) are logically proposed for the treatment of hypertension and heart failure because of their effect on reducing arteriol resistance. When administered early after myocardial infarction, CEI reduce mortality, particularly patients with severely deteriorated myocardium. Up to 74 lives can be saved for every 1000 patients treated. This beneficial effect is additive with that resulting from aspirin, beta-blockers and fibrinolysis. The effect occurs within the first month of treatment if initiated within the first 24 hours following the infarction, and persists even if treatment is discontinued. Tolerance is generally good, but dosage must be adapted in case of hypotension or temporary renal failure. Macroproteinuric nephropathy in insulin-dependent-diabetes is another indication for CEI. Captopril and enalapril have been shown to slow progression of renal failure and decrease the risk of death and of chronic dialysis. Further studies are being conducted to determine the effect of CEI in non-insulin-dependent diabetes. Finally, experimental arguments suggest that atherosclerosis is partly dependent on the renin/angiotensin system and that CEI might inhibit its development. Most clinical trials evaluating the action of CEI on atheromatosis have studied the effect in the carotid and coronary arteries.
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PMID:[Enzyme converting inhibitors. Current knowledge and perspectives]. 854 40


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