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

It is clear that cocaine has cardiotoxic effects. Acute doses of cocaine suppress myocardial contractility, reduce coronary caliber and coronary blood flow, induce electrical abnormalities in the heart, and in conscious preparations increase heart rate and blood pressure. These effects will decrease myocardial oxygen supply and may increase demand (if heart rate and blood pressure rise). Thus, myocardial ischemia and/or infarction may occur, the latter leading to large areas of confluent necrosis. Increased platelet aggregability may contribute to ischemia and/or infarction. Young patients who present with acute myocardial infarction, especially without other risk factors, should be questioned regarding use of cocaine. As recently pointed out by Cregler, cocaine is a new and sometimes unrecognized risk factor for heart disease. Acute depression of LV function by cocaine may lead to the presence of a transient cardiomyopathic presentation. Chronic cocaine use can lead to the above problems as well as to acceleration of atherosclerosis. Direct toxic effects on the myocardium have been suggested, including scattered foci of myocyte necrosis (and in some but not all studies, contraction band necrosis), myocarditis, and foci of myocyte fibrosis. These abnormalities may lead to cases of cardiomyopathy. Left ventricular hypertrophy associated with chronic cocaine recently has been described. Arrhythmias and sudden death may be observed in acute or chronic use of cocaine. Miscellaneous cardiovascular abnormalities include ruptured aorta and endocarditis. Most of the cardiac toxicity with cocaine can be traced to two basic mechanisms: one is its ability to block sodium channels, leading to a local anesthetic or membrane-stabilizing effect; the second is its ability to block reuptake of catecholamines in the presynaptic neurons in the central and peripheral nervous system, resulting in increased sympathetic output and increased catecholamines. Other potential mechanisms of cocaine cardiotoxicity include a possible direct calcium effect leading to contraction of vessels and contraction bands in myocytes, hypersensitivity, and increased platelet aggregation (which may be related to increased catecholamine). The correct therapy for cocaine cardiotoxicity is not known. Calcium blockers, alpha-blockers, nitrates, and thrombolytic therapy show some promise for acute toxicity. Beta-Blockade is controversial and may worsen coronary blood flow. In patients who develop cardiomyopathy, the usual therapy for this entity is appropriate.
 ...
PMID:The effects of acute and chronic cocaine use on the heart. 134 9

Primarily hypervolaemic, high output forms of hypertension, with features indicating or strongly suggesting fluid overload as the cause of elevated cardiac output, resulting from renal disease with reduced glomerular filtration rate causing sodium retention, renal tubular causes of sodium retention, greatly excessive sodium intake and low renin hypertension, can be treated by reduction of sodium intake and potentiation of its excretion by diuretic therapy, removal of the cause (e.g. aldosteronoma), and calcium antagonists. Excessive vasoconstriction resulting from noradrenaline (norepinephrine) in neurogenic hypertension, phaeochromocytoma, orthostatic hypertension and alpha-adrenergic drug administration; angiotensin excess due to renal ischaemia brought about by aortic coarctation, renal arterial and arteriolar stenosis, intraluminal obstruction, external renal compression, renin-producing tumours, intrinsic kidney diseases and excessive renin substrate; and vascular structural disorders such as atherosclerosis, arteriolitides and fibrosis with or without calcification of major arteries may also induce hypertension. Secondary hypertension of uncertain mechanism may occur in hyperparathyroidism, hyper-or hypothyroidism, or acromegaly. All are best treated by appropriate correction of the endocrine excess or deficiency. It may also occur in pregnancy, where the mechanism may involve prostaglandin-thromboxane imbalance or calcium deficiency; calcium deficiency with some evidence of benefit from calcium supplements; and the recumbent hypertension paradoxically associated with autonomic failure. Excellent responses to specific correction of the underlying cause or pathogenetic mechanism is usual in young individuals but less frequent in older patients.
 ...
PMID:Secondary hypertension. An overview of its causes and management. 137 54

Factors that can influence cardiovascular growth are becoming increasingly important for our understanding of such complex diseases as cardiac hypertrophy, coronary artery disease, atherosclerosis, and hypertension. Several proto-oncogenes were found to be involved in the regulation of abnormal cell growth in cardiovascular disease. It is also evident that some peptide hormones, which are well known to be involved in blood pressure control, may play a role as growth modulators. Angiotensin II is one such peptide. It elevates blood pressure through its direct vasoconstrictor, sympathomimetic, and (through release of aldosterone) sodium-retaining activity but also appears to have mitogenic actions. Interestingly, all components of the renin-angiotensin system were found locally in cardiovascular tissues. The question remains whether angiotensin can act directly as a growth factor or whether it does so indirectly by influencing or modulating cell growth factors. A better understanding of the renin-angiotensin system as a direct or indirect mediator for cardiovascular hypertrophy would offer new and interesting insights into the pathophysiology of hypertension and possibly novel options for the treatment of cardiovascular disease.
 ...
PMID:The molecular basis of cardiovascular hypertrophy: the role of the renin-angiotensin system. 138 95

Vascular responses to intraluminal and abluminal activation of human platelets were examined in carotid arteries from normal and atherosclerotic rabbits. The carotid artery was perfused in vitro, platelets were activated with thrombin (0.1 unit/ml), and changes in diameter were measured. In vessels from normal animals, intraluminal activation of platelets produced dilatation of preconstricted arteries. The dilator response was attenuated by N omega-nitro-L-arginine (10(-5) M), an inhibitor of synthesis of endothelium-derived relaxing factor-nitric oxide (EDRF-NO), and augmented by LY53,857 (10(-5) M), a 5-HT2-serotonergic antagonist. Abluminal activation of platelets produced modest constriction in quiescent arteries, which was inhibited by LY53,857. Intraluminal but not abluminal ADP produced pronounced dilatation of preconstricted arteries. In vessels from atherosclerotic animals, endothelium-dependent dilatation to intraluminal activation of platelets and to ADP was impaired and dilator responses to sodium nitroprusside were normal. These experiments indicate that 1) intraluminal activation of human platelets produces endothelium-dependent dilatation in perfused carotid arteries, whereas abluminal activation of human platelets produces vasoconstriction, which is mediated primarily by serotonin, and 2) atherosclerosis markedly impairs vasodilator responses to activation of human platelets, probably because vasodilatation to ADP released from platelets is impaired.
 ...
PMID:Effect of atherosclerosis on responses of the perfused rabbit carotid artery to human platelets. 139 May 92

Isolated systolic hypertension (ISH) is generally defined as a systolic pressure of 160 mmHg or more, with a diastolic pressure cut-off point below 95 mmHg in some studies and 90 mmHg in others. Its prevalence and incidence vary from 3 to 30% depending on the definition applied, methodology of measurement, as well as the population and the age and sex of the patients. Mechanisms that could lead to the development of isolated systolic hypertension are discussed, especially the role of atherosclerosis and sodium intake. Comparing results from different countries, the Intersalt study showed that the age related rise in systolic pressure was positively related to the mean sodium excretion in that country. A post-hoc analysis of data from 4 Belgian groups could not show such a correlation within our country. The risks of systolic hypertension on mortality and morbidity in the elderly are considered. The need for further studies to quantify the risk and to establish the effect of treatment is emphasized. Three such studies in patients above the age of 60 years with ISH were started. The studies are double-blind, placebo-controlled trials and the main purpose is to examine the influence of treatment on morbidity, mortality, and general well-being. In the American SHEP study the patients of the actively treated group received a diuretic and possibly a beta-blocker or reserpine. The results indicate a significant reduction in non fatal stroke, heart failure and myocardial infarction without a significant reduction in fatal stroke, fatal myocardial infarction, cardiovascular or all cause mortality. Studies in other continents are still in progress, such as the Syst-Chin in China and the Syst-Eur trial in Europe. They may indicate whether the results obtained in the U.S.A. can be extrapolated to other continents and whether the use of other drugs without metabolic disturbances, such as calcium entry blockers and angiotensin converting enzyme inhibitors, produce a similar reduction in events. Additional studies are needed to establish the effect of reducing salt intake in younger age groups on the prevalence of ISH and of the related morbidity and mortality.
 ...
PMID:[Isolated systolic hypertension in persons older than 60]. 141 81

The renin-angiotensin system (RAS) plays a major role in the control of blood pressure and cardiovascular homeostasis and is involved in the pathogenesis of a number of cardiovascular disorders. The efficacy of angiotensin-converting enzyme (ACE) inhibitors in the treatment of hypertension and congestive heart failure has led to the widespread clinical use of ACE inhibitors in primary or secondary prevention of heart disease. The demonstration of the expression of the components of the RAS in several extrarenal tissues, as well as local generation of angiotensin II, has confirmed the existence of a tissue RAS that may serve organ-specific functions and act independently from the plasma RAS. The concept of paracrine/autocrine functions of the local RAS has changed our understanding of the functions of the RAS and suggests that tissue ACE inhibition may be of greater importance than inhibition of circulating ACE in the treatment of congestive heart failure and other cardiovascular disorders. Whereas the circulating endocrine RAS appears to be responsible for mediation of acute effects, the tissue RAS seems to be involved in more chronic situations, such as secondary structural changes of the cardiovascular system, and therefore could contribute to the pathogenesis of hypertension as well as other cardiovascular disorders, such as cardiac hypertrophy, coronary artery disease, and atherosclerosis. Several experimental and clinical findings suggest that reversal of cardiovascular structural changes secondary to cardiovascular disease and enhancement of renal sodium excretion by ACE inhibitors are important long-term antihypertensive actions possibly mediated by inhibition of the tissue RAS.
 ...
PMID:Effects of angiotensin-converting enzyme inhibitors on tissue renin-angiotensin systems. 141 88

Na+/H+ exchange rate in erythrocytes of patients with atherosclerosis of lower limb arteries is less than in erythrocytes of healthy subjects. Ultraviolet exposure of the patients blood in vitro activates Na/H exchange in erythrocytes.
 ...
PMID:[Effects of ultraviolet irradiation on the Na/H exchange rate in erythrocytes of healthy subjects and patients with atherosclerosis of lower limb arteries]. 147 42

Coronary Heart Disease (CHD) is less common in females compared to males and geographical differences are observed in both sexes; furthermore time trend mortality in women follows the same pattern as in men suggesting that the environmental factors have similar influence in both sexes. Nutrition is an environmental factor which plays an important role in the etiology and pathogenesis of CHD. The Italian Nine Communities Study on Atherosclerosis Risk Factors analyzes the relationships between consumption of food rich in saturated fatty acids and cholesterol and a number of CHD risk factors in a sample of Italian women aged 20-59 years. The dietary habits of the participants were ascertained by a food frequency questionnaire. Intake of atherogenic food was evaluated for each participants systolic blood pressure, serum glucose, serum cholesterol increased with increasing consumption of atherogenic food (i.e. butter). Conversely, consumption of olive oil and vegetable oil was inversely associated with serum cholesterol, serum glucose and systolic blood pressure. Furthermore, calcium rich food consumption was associated with lower blood pressure. These findings were independent from any possible confounding effect of age, adiposity, alcohol intake and cigarette smoking. Data from the Intersalt Study in Italy (400 women aged 20-59 years) have clearly shown lower blood pressure levels in participants with lower intake of sodium and alcohol and higher intake of potassium. Some clinical and experimental observations suggest a possible difference in response to dietary factors in women compared to men due to the intermediate effects of the sex hormone pattern.
 ...
PMID:[Diet and cardiovascular risk among women in Italy]. 149 32

The author reviews findings assembled during the last 20 years on the endothelium-derived relaxing factor (EDRF), and in particular findings assembled the last five years which revealed that EDRF is identical with nitric oxide, NO. The enzyme NO synthetase produces NO from l-arginine with the concurrent formation of citrulline and is present not only in the endothelium of the vascular wall but also in cerebral neurons and other tissues. NO is probably also the effective factor of the vasodilatating action of organic nitrates (nitroglycerol, amyl nitrite, sodium nitroprusside). In recent years these findings are applied also in clinical work. In atherosclerosis of the coronary vessels NO formation is obviously reduced and l-arginine infusion may improve the coronary blood supply in patients with hypercholesterolaemia. Inhalation of NO has been tried in pulmonary hypertension. Antidotes of NO (methylene blue) conversely may prevent hypotension in hepatic failure. Infusion of an antidote of l arginine prevents hypotension in septic shock. This is due to the fact that an excess of NO is formed from macrophages during infections. NO is, however, also mutagenic and there are reports on its participation in the genesis of genetic and neoplastic diseases.
 ...
PMID:[EDRF-NO. The endothelium-derived relaxing factor is nitric oxide]. 150 92

Normal New Zealand and Watanabe heritable hyperlipidemic (WHHL) rabbits, about 24 months old, were prepared, under anaesthesia, for recording blood pressure and hindlimb blood flow. Changes in hindlimb vascular resistance were measured after local intra-arterial bolus injection of increasing doses of acetylcholine, bradykinin, serotonin, sodium nitroprusside and phenylephrine. In WHHL rabbits basal hindlimb blood flow was reduced (from 22.6 +/- 3.0 to 12.5 +/- 1.8 ml/min; P less than 0.05) and hindlimb vascular resistance was increased (from 4.6 +/- 0.5 to 8.2 +/- 1.5 mmHg/ml per min; P less than 0.05). No difference was observed in response to acetylcholine, serotonin, sodium nitroprusside and phenylephrine. The only marked alteration found in WHHL rabbits was a clear deficit to bradykinin stimulation. Morphological analysis, using scanning and transmission electron microscopy, indicated a clear damage of the femoral artery, like the presence of atherosclerotic plaques, and an abnormal distribution of patent microvessels in the WHHL muscles of the leg. Peripheral circulation in WHHL rabbits shows some peculiar features, like increased basal vascular resistance and a selective impairment of bradykinin responses. Together with these abnormalities, it seems that responses to various other dilating or contracting agents are normal, suggesting that in this interesting animal model of atherosclerosis the alterations are more specific than in other models.
Atherosclerosis 1992 Mar
PMID:Functional responses of hindlimb circulation in aged normal and WHHL rabbits. 159 96


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>