Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension develops in most patients after transplantation when immunosuppression is based on cyclosporine and prednisone. The pathogenesis appears to be multifactorial but involves rapidly rising vasoconstrictor tone in renal and systemic vascular beds. Much of this tone reflects abnormal vascular function, characterized by impaired prostacyclin and EDRF effects, in conjunction with increased vasoconstriction due to endothelin and possibly other factors. Effective management of the transplant recipient depends on preventing excessive vasoconstriction, usually with calcium channel blocking agents.
Hypertension 1993 Aug
PMID:De novo hypertension after liver transplantation. 834 Jan 62

Endothelin-1 may function pathophysiologically as a counterregulatory vasoconstrictor peptide that is modified in its activity by the opposing action of endothelium-derived relaxing factor(s) (EDRF). The present study determined in part the integrated cardiorenal and endocrine actions of pathophysiologic plasma concentrations of endothelin in the anesthetized dog. In addition, nitroglycerin, which inhibits vascular smooth muscle contraction by increasing cGMP in a mechanism similar to EDRF, acts like an endogenous nitrovasodilator. Therefore, we tested the hypothesis that nitroglycerin would effectively antagonize the cardiac and renal actions of exogenous endothelin. The results confirm that endothelin-1-mediated vasoconstriction in vivo is heterogenous with a greater renal than coronary action. Further, nitroglycerin effectively blocked endothelin-1-mediated coronary flow reductions, but only partially antagonized reductions in renal blood flow. Endothelin-1-induced reduction in cardiac output also was not antagonized by nitroglycerin despite its effects to preserve coronary blood flow. Nitroglycerin did, however, antagonize endothelin-induced elevations in plasma epinephrine, norepinephrine, and aldosterone. These results would suggest that in pathophysiologic states where endothelin-1 is elevated, such as hypertension or congestive heart failure, there is a major compromising of renal function, and also the production of cardiac ischemia. Since exogenous nitroglycerin is relatively ineffective in antagonizing the renal vasoconstrictive effects of endothelin, it may be that the endogenous vasodilating systems, such as ERDF and prostacyclin, are inadequate in such pathologic states to counter the vasoconstrictor effects of endothelin.
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PMID:Endothelin-mediated cardiorenal hemodynamic and neuroendocrine effects are attenuated by nitroglycerin in vivo. 838 58

The endothelium can respond to a local environment by releasing a variety of substances that regulate the level of vascular tone. One of the most important of these vasoregulatory substances is EDRF. The function of the endothelium is altered in a variety of pathologic and physiologic conditions. This review focused on the role of risk factors for atherosclerosis as it relates to EDRF. Atherosclerotic blood vessels respond abnormally on exposure to stimuli that release EDRF. It is now also apparent that this abnormal vascular response may precede the development of significant atherosclerosis and that normalization of the EDRF response with treatment is possible. Thus abnormal endothelium-dependent relaxation has been demonstrated in hypercholesterolemic patients with little or no evidence of coronary angiographic disease and in patients with hypertension before the development of atherosclerosis. The interaction between risk factors and the function of the vascular endothelium with development of atherosclerosis may become a useful focus for therapies that benefit patient outcomes.
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PMID:Atherosclerosis: risk factors and the vascular endothelium. 857 37

The plasmid pMK16 containing-SV40 replicated origin defective gene was efficiently introduced into early-passage human umbilical vein endothelial cells (HUVEC) using positively charged liposomes. The resulting cell line acquired an almost infinite lifespan, was morphologically unchanged, expressed SV40-antigen, and coexpressed von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), angiotensin conversion enzyme (ACE), and endothelin converting enzyme (ECE). In addition, these are the first immortalized human endothelial cells, to our knowledge, that biosynthesized and secreted interleukins (IL-1 beta and IL-6) in both a constitutive and regulated fashion and endothelin-1 (ET-1), the most potent vasoactive peptide, which has been suggested to be implicated in the pathogenesis of hypertension. Interestingly enough, both of the immortalized cells and the early-passage HUVEC from which the immortalized cells were obtained biosynthesized and secreted the same levels of ET-1 suggesting full maintenance of its biosynthetic pathway including the presence of active ECE, which cleaves big endothelin-1 (big-ET-1) to ET-1 and regulation factors. Moreover, the immortalized cells retained the ability to express the functional specific amino acid Na(+)-independent system Y+ transporter, which mediates L-arginine transport into endothelial cells from which endothelium-derived relaxing factor (EDRF, nitric oxide) is formed via the action of nitric oxide-synthase. Obtaining these immortalized human endothelial cells without alteration of the differentiated characteristics constitutes a useful model: (a) to study ET-1 secretion, gene regulation, and human ECE, which may be an important therapeutic target in disease conditions in which ET-1 is to be implicated; (b) to study L-arginine transport, which is a key step in the formation of EDRF; (c) to study IL-1 beta and IL-6 secretions, and gene regulations; (d) to substitute large quantities of HUVEC; and, finally, (e) to reproduce, starting with different primary endothelial cells both from human and animal origin.
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PMID:Establishment of permanent human endothelial cells achieved by transfection with SV40 large T antigen that retain typical phenotypical and functional characteristics. 883 14

For about 120 years we have been looking for the 'cause' of essential hypertension. It is possible that we have merely been wandering through its graveyard, looking at the pathogenetic mechanisms but never the actual cause? Here we pass the gravestone of increased sympathetic activity; there the gravestone of low renin activity. Here high endothelin; there low EDRF. Here high thromboxane A2; there low prostacyclin. It is possible that all these and so many other pathogenetic factors are all due to one basic defect? Is it possible that, in the dead of night while patients with EH have been sleeping, the villain has been lurking in their mouths, stuck somewhere at the back of their throats, hidden from view yet choking them hundreds of times a night. But this intermittent strangulation has not occurred silently. On the contrary, it has made its presence felt in the most irritating way, with snores, groans, grunts, gasps and frightening periods of total apnea. But we, their physicians, never asked about these symptoms, or, if we did, we never paid heed to them. This is clear from the fact that, most cases of OSA occur in association with EH yet are not diagnosed. Perhaps the next 'arousal response' should be the arousal of physicians' consciousness so that they can at long last wake up to the existence of the close connection between sleep-related breathing disorders and hypertension and breathe some new life into the treatment of two old diseases-essential hypertension and secondary hypertension. Early diagnosis and treatment of the sleep-related breathing disorders may not only make the patient feel much better, (something our antihypertensive medications do not always do), but may reduce the blood pressure and prevent the progression of renal and cardiovascular damage as well.
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PMID:Sleep-related breathing disturbances: their pathogenesis and potential interest to the nephrologist. 914 Sep 93

Since the classical studies by Furchgott and Zawadski (Nature, 1980, 286, 373-376), the vascular endothelium is known to play a fundamental role in the regulation of haemostasis and vasomotor activity. This is primarily due to its strategic interface position between the circulating blood and smooth muscle cells of the media. Due to the presence of specific receptors to mediators released during platelet aggregation (thrombin, ATP, serotonin, PAF, etc.), and the presence of mechanoreceptors sensitive to shearing forces generated by blood flow along the vessel wall, the endothelium is able to release, at the two poles of the cell, vasodilator and antiaggregant substances called "endothelium derived relaxing factors" (EDRFs), the best known for which are nitric oxide (NO) ans prostacyclin (PGl2). In the absence of endothelium (angioplasty), or in the case of endothelium dysfunction related to cardiovascular diseases such as hypertension, heart failure, atherosclerosis or diabetes, EDRF synthesis is absent or defective and its oxidative catabolism in increased (particularity by superoxide anion), resulting in varying degrees of disorders of haemostasis (thrombosis) and/or arterial and venous vasomotor activity. The only known effective treatment to palliate these dysfunctions is exogenous NO, supplied in the form of nitrate (nitroglycerin, isosorbide dinitrate, 5-mononitrate) or "NO donors" (Sin1, nitroprussate). The advantage of these substances is that their vasodilator effects (and, in some cases, their antiaggregant effects) are strictly endothelium-independent and they remain effective regardless of the causes and severity of endothelial dysfunction.
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PMID:[Nitrates and coronary vascular endothelium dysfunction]. 945 72

The vascular endothelial cell is a multipotent cell which has several functions: transport barrier, phagocytosis, coagulation/anticoagulation, fibrinolysis, autocrine/paracrine and metabolic functions. The release of vasoactive agents, such as the vasodilators EDRF (NO) and EDHF, and vasoconstrictors, such as endothelin (ET), represents an important local mechanism altering the balance of vasodilation/ vasoconstriction of the vascular smooth muscle cell. Inhibition of the synthesis of NO by exogenous (e.g. L-NAME) or endogenous (e.g. ADMA) L-arginine analogues may cause transient or sustained hypertension. A similar effect may be achieved by continuous administration of the potent vasoconstrictor ET. Endothelial dysfunction, associated with a deficient NO production and release as well an enhanced ET generation, may be present in some forms of vascular disease, such as hypertension, atherosclerosis, diabetes mellitus or sleep apnea. Whether such alterations may be a cause of hypertension and involved in the maintenance of high blood pressure or whether they represent a consequence of the hypertensive disease remains to be concluded. Furthermore, while there is emerging evidence that endothelial dysfunction in cardiovascular disease may be reversed by therapy, it remains to be determined whether measures of endothelial function in man may serve as predictors for morbidity or mortality.
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PMID:Measures of endothelial function as an endpoint in hypertension? 949 29

It has been proposed repeatedly that essential hypertension as well as secondary hypertension is associated in a causative manner with endothelial dysfunction in the resistance vessels. Endothelial damage and dysfunction may be expected to attenuate the endogenous vasodilator mechanism of EDRF (nitric oxide) and hence cause a rise in blood pressure. This attractive hypothesis, put forward a few years ago, is subject to considerable debate at present. In the present survey the arguments in favour and against this hypothesis are critically discussed. The following arguments support the causative association between endothelial dysfunction: the hypertensive effect of NO-synthase blockade by L-NAME and related agents; the antihypertensive effect of L-arginine in salt-loaded Dahl rats; the impaired vasodilator effect in the forearm vascular bed of hypertensives; diminished NO-synthesis in hypertensives. However, several findings speak against the association between hypertensive disease and endothelial dysfunction. For instance: no clear demonstration of impaired endothelial function in isolated vessels of hypertensive patients and animals; studies in the human forearm vascular bed where endothelial function appears to be fully intact in hypertensives. Attempts are made to explain the discrepancies between the various findings. So far the association between endothelial dysfunction and hypertension appears to be an uncertain one.
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PMID:Endothelial dysfunction in hypertension. A critical evaluation. 949 30

At the opportunity of the 100th anniversary of S. Riva-Rocci's publications on the new sphygmomanometer the author presents a review of the main publications which made this method possible and a review of clinical and pathological studies which led to the recognition of essential hypertension (EHT). He also mentions main adopted criteria of hypertension and draws attention to the difficulties associated with a definition and classification of EHT because of the variations in pressure and differences of "normal" values in various populations. From multicentre intervention studies precise and generally valid criteria for individual treatment cannot be derived. As to recent of work on the pathogenesis of EHT the author draws attention to the importance of endothelin and NO (EDRF), which play a part in the genesis of changes in the vascular wall in atheromatosis and also in hypertension. A new discovery is the bond between NO and haemoglobin (S-nitrosohaemoglobin). In addition to proved and located genetic factors also external factors are involved, in particular psychosocial factors, diet, body weight, smoking etc. on which prevention and treatment must be focused. Medicamentous treatment markedly improves the prognosis of hypertension. Antihypertensive drugs from all main groups of drugs are used. Dosage still remains an open question which cannot be resolved completely on the basis of intervention trials. ACE-inhibitors hold an important place--they reduce the blood pressure and also prevent progression of left ventricular hypertrophy. Beta-blockers and diuretics still remain the basis of first line treatment. Among Ca-inhibitor, preparation with long-term action are preferred. Open questions include--apart from dosage--the comparison of the efficacy/side effects ratio of new effective drugs (A I, A II, renin) and older antihypertensive drugs when used on a long-term basis; furthermore the justification to administer vasodilatating drugs as monotherapy and in combinations during long-term treatment with regard to the activation of the sympathetic nerve and risk of hypotension. The author discusses the sympathetic activation to which BP should be reduced and thus also the question of doses reduction and discontinuation of the drug--in particular in old patients. And finally, the role of hypertension as the sole cause of increased mortality (EEHT per se) must be proved. In practice the problems of the detection rate, adherence, information and correct treatment are of major importance.
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PMID:[100 years of hypertension]. 951 Dec 69

The endothelium is a major regulator of vascular tone, releasing vasoactive substances such as endothelium-derived nitric oxide (EDRF), endothelium-derived hyperpolarizing factor(s), cycloxygenase metabolites, endothelin and other endothelium-derived contracting factors (EDCF). In a number of cardiovascular pathologies, such as hypertension or heart failure, the balance in the endothelial production of vasodilating and vasoconstricting mediators is altered. The resulting apparent decrease in endothelium-dependent relaxations is termed 'endothelial dysfunction'. In hypertensive patients and in animal models of hypertension, endothelium-dependent relaxations are impaired. However, this endothelial dysfunction presents different characteristics depending on the model studied. In Dahl-salt-sensitive rats, the decrease in endothelium-dependent relaxations is associated with impaired constitutive nitric oxide synthase activity. The presence of an endogenous nitric oxide synthase inhibitor and a decreased response of vascular smooth muscle to the mediator may contribute also to the dysfunction observed in this model. In other animal models of hypertension (such as spontaneous hypertension). the contribution of the L-arginine nitric oxide pathway to endothelium-dependent responses appears normal or impaired despite reports of increased nitric oxide synthase activity or expression. In large arteries from SHR, endothelium-dependent relaxations are impaired mainly because of the concomitant augmented release of endoperoxides activating thromboxane-endoperoxide receptors. Superoxide anions may also play a role in some models, but only in the early phase of the disease: whether or not these species contribute to further development of endothelial dysfunction or to increases in blood pressure remains to be examined. The endothelial dysfunction observed in hypertension is likely to be a consequence of high blood pressure. but it could facilitate the maintenance of elevated peripheral resistance at a later stage in the disease and favour the occurrence of complications, such as atherosclerosis.
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PMID:Secondary endothelial dysfunction: hypertension and heart failure. 1007 14


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