Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007222 (cardiovascular disease)
 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a source of several vasoactive factors, the endothelium takes part in the regulation of vascular tone. The most important endothelium-derived vasoactive substances are nitric oxide, prostacyclin, endothelin-1 and contracting factors requiring the activity of cyclooxygenase. The endothelium is an obvious target organ of cardiovascular risk factors. Accordingly, functional alterations do occur with aging, hypertension and hypercholesterolaemia. All three conditions are associated with a decreased basal and simulated release of endothelium-derived nitric oxide. On the other hand, the release of endothelin-1 appears to increase with age, while the sensitivity to the peptide markedly decreases under the same conditions. In the spontaneously hypertensive rat, acetylcholine and stretch evoke the release of a cyclooxygenase-dependent endothelium-derived contracting factor, most likely prostaglandin H2. The circulating levels of endothelin-1 on the other hand are not increased in experimental and human hypertension. In the porcine coronary circulation, oxidized low-density lipoproteins selectively reduced endothelium-dependent relaxations to aggregating platelets, serotonin and thrombin which are mediated by nitric oxide. The alterations of endothelial function occurring with aging, hypertension and hypercholesterolaemia may have important clinical implications for the pathogenesis of cardiovascular disease.
 ...
PMID:Age, hypertension and hypercholesterolaemia alter endothelium-dependent vascular regulation. 150 46

Thromboxanes are cyclooxygenase products of C-20 polyenoic fatty acids. The arachidonic acid derivate, thromboxane A2 (TXA2), is the only biologically relevant product and is mainly generated in blood platelets. Hyperreactivity of blood platelets appears to be an important risk factor for thromboembolic vessel occlusion in the presence of preexisting vascular pathology. Starting with acetylsalicylic acid, which is still the reference standard, several attempts have been made over the past few years to develop more specific drugs which selectively modify platelet TXA2 formation, a most important feedback-stimulator of platelet function. Thromboxane synthase inhibitors were the first compounds which were tested clinically. Some data suggest beneficial effects in several types of cardiovascular disease. However, the overall impression is that the compounds available so far may not be superior to acetylsalicylic acid. Thromboxane receptor antagonists and mixed type synthase inhibitor/receptor blocking compounds would appear to be more promising from a theoretical point of view. These compounds exhibit a number of beneficial effects in animal studies. However, clinical experience so far is very limited. It is concluded that fresh insight into the regulation and types of thromboxane receptors, the development of long-lasting synthase inhibitors, non-competitive thromboxane receptor antagonists and combined mode-active drugs, as well as a better understanding of interactions between several classes of platelet-active mediators (prostacyclin, nitric oxide, PAF) will probably result in improved drug treatment of ischaemic cardiovascular disease in the near future.
 ...
PMID:[Thromboxane antagonism in thrombocytes--pathophysiology, pharmacology and possible clinical significance]. 183 94

As a source of several vasoactive factors, the endothelium takes part in the regulation of vascular tone. The most important endothelium-derived vasoactive substances are nitric oxide, prostacyclin, endothelin-1 and contracting factors requiring the activity of cyclooxygenase. The endothelium is an obvious target organ of cardiovascular risk factors. Accordingly, functional alterations do occur with aging, hypertension, and lipids. All three conditions are associated with a decreased basal and stimulated release of endothelium-derived nitric oxide. On the other hand, the release of endothelin-1 appears to increase with age, while the sensitivity to the peptide markedly decreases under the same conditions. In the spontaneously hypertensive rat, acetylcholine and stretch evoke the release of cyclooxygenase-dependent endothelium-derived contracting factor, most likely prostaglandin H2. The sensitivity and circulating levels of endothelin-1, on the other hand, are reduced in this experimental model of hypertension. In the porcine coronary circulation, oxidized low-density lipoproteins selectively reduce endothelium-dependent relaxations to aggregating platelets, serotonin, and thrombin which are mediated by nitric oxide. The alterations of endothelial function occurring with aging, hypertension, and hyperlipidemia may have important clinical implications for the pathogenesis of cardiovascular disease.
 ...
PMID:Endothelium-dependent control of vascular tone: effects of age, hypertension and lipids. 195 6

Knowledge of the connection between habitual snoring diseases and obstructive sleep apnoea has stimulated research into sleep disturbance in patients at high risk of cardiovascular disease. Any disturbance of nasal ventilation leads to a higher resistance to breathing and may cause cardiovascular complications in the long run. Anatomical and functional conditions that lead to intermittent incomplete blockage or complete occlusion of the upper respiratory tract must be detected and surgically eliminated, if possible. Surgical procedures for treating snoring and obstructive sleep apnoea may be successful and fill the gap between conservative treatment and continuous nasal positive airway pressure therapy. Our experience in 24 patients in presented.
HNO 1991 Apr
PMID:[Experience with surgical therapy in snoring and sleep apnea]. 206 69

The endothelium releases a variety of factors which can affect vascular tone. Endothelium-derived relaxing factor or nitric oxide is a very potent vasodilator and inhibitor of platelet function. Its release has been demonstrated in a variety of human blood vessels. In most human vascular preparations, prostacyclin does not significantly contribute to the endothelium-dependent relaxations. Prostacyclin is, however, an endothelium-derived product which can evoke vasodilation and inhibition of platelet aggregation. In addition, the endothelium of human veins can release endothelium-derived contracting factors produced by the cyclooxygenase pathway. Endothelin is an endothelium-derived vasoactive peptide which has profound vasoconstrictor properties in human arteries and particularly in veins. Its action can only be partially inhibited by calcium antagonists, while endothelium-derived nitric oxide and exogenous nitrovasodilators are effective antagonists of the peptide. The mechanisms and amounts of endothelin released in human blood vessels remains to be defined. Under physiological conditions, endothelium-derived relaxing factors appear to dominate. The release of endothelium-derived nitric oxide is reduced in atherosclerotic human arteries. This indicates that in cardiovascular disease endothelial dysfunction occurs; this may contribute in the pathogenesis of coronary artery disease, pulmonary hypertension and stroke.
 ...
PMID:Endothelium-derived vasoactive factors and regulation of vascular tone in human blood vessels. 216 86

An increased platelet-vessel wall interaction plays an important role in most forms of cardiovascular disease. In healthy arteries, the vascular endothelium prevents platelet adhesion and aggregation. As a mediator of this protective function, the endothelium produces prostacyclin, endothelium-derived nitric oxide and tissue plasminogen activator. Cardiovascular risk factors such as hypertension, hyperlipidemia and diabetes are associated with an increased platelet activation and with decreased antithrombotic properties of the blood vessel wall. The available inhibitors of platelet function interfere only with one of various mechanisms of platelet activation and of the platelet-vessel wall interaction. Prostaglandin inhibitors, such as aspirin and newer, more specific inhibitors, prevent the production and/or the effect of thromboxane A2 on platelets and the blood vessel wall. Other drugs interfere with the effect of adenosine diphosphate on platelets, or they increase intracellular concentration of cyclic GMP or AMP in platelets and vascular smooth muscle cells. The protective effects of platelet inhibitors in primary and particularly in secondary prevention of cardiovascular diseases have been documented in numerous studies. The successful clinical use of these substances, however, requires a selective prescription of the drugs in patients with cardiovascular disease.
 ...
PMID:[Thrombocyte inhibitors in cardiovascular therapy]. 221 49

The endothelium modulates coronary vascular tone by the release of endothelium-derived relaxing or contracting substances. The endothelium-derived relaxing factor has been identified as nitric oxide synthesized in endothelial cells from L-arginine. The endothelium can release other relaxing substances such as prostacyclin and a hyperpolarizing factor. Endothelin-1 is a potent vasoconstrictor peptide formed by endothelial cells, and is likely to be the physiologic antagonist of endothelium-derived relaxing factor. Other putative contracting factors include superoxide anions and products of arachidonic acid metabolism. Endothelium-derived relaxing factor is released spontaneously and in response to flow, platelet-derived products (that is, serotonin, thrombin and adenosine diphosphate) and certain autacoids (that is, acetylcholine, bradykinin, histamine, substance P, vasopressin, alpha-adrenergic agonists). A considerable heterogeneity of responses exists among vessels of different size from different anatomic origin and different species. Hypercholesterolemia, atherosclerosis, hypertension and myocardial ischemia or reperfusion, or both, impair endothelium-dependent relaxation. Under normal conditions, endothelium-derived relaxing factor appears to dominate the control of vascular tone of large and small coronary vessels, whereas in disease states, endothelium-derived contracting factors are released. Impairments of endothelial function may be important in the development of various forms of cardiovascular disease.
 ...
PMID:Endothelial control of vascular tone in large and small coronary arteries. 240 18

Epidemiologic evidence suggests that cigarette smoking is a major risk factor for chronic obstructive pulmonary diseases such as chronic bronchitis and emphysema, for carcinogenesis, and for cardiovascular disease. However, the precise mechanisms of these effects are incompletely understood. The gas phase of cigarette smoke contains abundant free radicals including nitric oxide. Hence, cigarette smoke may induce some of its damaging effects by free radical mechanisms. We report that exposure of plasma, a model for respiratory tract lining fluids, to gas-phase cigarette smoke causes depletion of antioxidants, including ascorbate, urate, ubiquinol-10, and alpha-tocopherol, and a variety of carotenoids, including beta-carotene. Gas-phase cigarette smoke induced some lipid peroxidation, as measured by cholesteryl linoleate hydroperoxide (18:2OOH) formation. Ascorbate was effective in preventing 18:2OOH formation. In contrast to the low concentrations of lipid hydroperoxides measured (< 1 mumol/L), protein carbonyl formation, a measure of protein modification, increased by approximately 400 mumol/L after nine puffs of cigarette smoke. Reduced glutathione inhibited protein carbonyl formation, whereas other plasma antioxidants, including ascorbate, were ineffective. alpha, beta-Unsaturated aldehydes (acrolein and crotonaldehyde) in cigarette smoke may react with protein -SH and -NH2 groups by a Michael addition reaction that results in a protein-bound aldehyde functional group. Gas-phase cigarette smoke is capable of converting tyrosine to 3-nitrotyrosine and dityrosine, indicating free radical mechanisms of protein damage by nitrogen oxides. Aldehydes and nitrogen oxides in cigarette smoke may be significant contributors to biomolecular damage, and endogenous antioxidants can attenuate some of these adverse effects.
 ...
PMID:Dietary antioxidants and cigarette smoke-induced biomolecular damage: a complex interaction. 749 50

The effects of cardiovascular drugs on endothelium and vascular smooth muscle function are important for the prevention of cardiovascular disease. Changes in endothelial function are an early event in most forms of cardiovascular disease and, later in the disease process, vascular smooth muscle cells are functionally altered and begin to migrate to and proliferate in the intima. Calcium antagonists and angiotensin converting enzyme (ACE) inhibitors are widely used in patients with cardiovascular disease and are thought to have vascular protective effects. ACE, an enzyme located in the endothelial cell membrane, activates angiotensin I and angiotensin II, and deactivates bradykinin. Bradykinin activates endothelial bradykinin (B2) receptors, which results in the formation of nitric oxide and prostacyclin. Hence, ACE inhibitors not only prevent the formation of angiotensin II, but also increase the local levels of bradykinin and in turn nitric oxide and prostacyclin. These compounds are vasodilators and potent inhibitors of platelet function, and therefore may mediate important protective effects of ACE inhibitors. Furthermore, nitric oxide may have antiproliferative effects in vascular smooth muscle cells. Calcium antagonists do not appear to affect the release of endothelium-derived relaxing factors or any other endothelial product. However, they facilitate endothelium-dependent relaxation and reduce the contracting effects of endothelin-1 at the level of smooth muscle. Indeed, in some blood vessels, e.g. the large coronary arteries and the human forearm circulation, verapamil and nifedipine antagonise endothelin-induced contractions. In addition, calcium antagonists inhibit the effects of platelet-derived growth factor and may have antiproliferative effects in vascular smooth muscle cells. In conditions involving progressive dysfunction of the endothelium, vascular deposition of platelets increases the local levels of platelet-derived growth factor, and the antiproliferative effects of calcium antagonists may thus be particularly important.
 ...
PMID:Calcium antagonists and ACE inhibitors. Effect on endothelium and vascular smooth muscle. 751 65

Cigarette smoking is associated with an increased risk of respiratory tract infections, chronic airway disease, and cardiovascular diseases, all of which may be modulated by endogenous nitric oxide (NO). We have investigated whether cigarette smoking reduces the production of endogenous NO. We compared exhalations of 41 current cigarette smokers with normal lung function and 73 age-matched non-smoking controls. Peak exhaled NO levels were measured by a modified chemiluminescence analyzer. The effects of inhaling a single cigarette in smokers were also measured. In control subjects we also measured the effects of inhalation of NO itself and carbon monoxide, both constituents of tobacco smoke. Peak exhaled NO concentrations were significantly reduced in smokers (42 +/- 3.9 compared with 88 +/- 2.7 parts per billion in nonsmokers, p < 0.01), with a significant relation between the exhaled NO and cigarette consumption (r = 0.77, p < 0.001). Smoking a single cigarette also significantly (p < 0.02), but transiently, reduced exhaled NO. Inhalation of carbon monoxide and NO had no effect on exhaled NO in normal subjects. Cigarette smoking decreased exhaled NO, suggesting that it may inhibit the enzyme NO synthase. Since endogenous NO is important in defending the respiratory tract against infection, in counteracting bronchoconstriction and vasoconstriction, and in inhibiting platelet aggregation, this effect may contribute to the increased risks of chronic respiratory and cardiovascular disease in cigarette smokers.
 ...
PMID:Acute and chronic effects of cigarette smoking on exhaled nitric oxide. 754 45


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