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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renin angiotensin system (RAS) is now recognized as the body's most powerful hormone system for controlling renal hemodynamics and sodium excretion and, therefore, body fluid volumes and arterial pressure. The discovery of angiotensin converting enzyme inhibitors (ACEi) was a keystone for the understanding of the significance of the RAS since ACEi proved to be effective in controlling hypertension and heart failure and in preventing the development of the vascular injury of chronic diseases like scleroderma and diabetes mellitus. The success of ACEi stimulated the research into inhibitors of other actors of the RAS like renin or angiotensin receptor antagonists. It is not often realized that the discovery of ACEi owes a great deal to basic research in which the venom of a Brazilian viper, Bothrops Jararaca, was instrumental for the discovery of bradykinin by Rocha e Silva and the bradykinin potentiating factor. This article reviews the contribution of the converting enzyme inhibitors for the demonstration of the relevance of the RAS to several human pathologies.
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PMID:Angiotensin converting enzyme: history and relevance. 1070 50

Hypertension is often referred to as the "silent killer" because most hypertensive patients are asymptomatic until cardiovascular sequelae such as stroke, myocardial infarction, heart failure, or renal failure occur. LVH is a common finding in patients with hypertension, especially African-Americans. Data from the Framingham Heart Study indicate that LVH is an independent risk factor for major cardiovascular events. In the Amlodipine Cardiovascular Community Trial, 37% of 124 hypertensive patients screened by means of echocardiography had LVH at baseline. Although there was no difference in the prevalence of LVH by gender or age, African-American patients were nearly twice as likely to have LVH than white patients (64% vs. 34%, p<0.05). Hence, aggressive therapy to reach target goals outlined in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) is especially important in this group of patients. Even lifestyle modifications such as weight reduction and limitation of salt intake, if sufficiently aggressive, can lead to regression of LVH, as demonstrated by results of the Treatment of Mild Hypertension Study (TOMHS). Most classes of antihypertensive drugs are effective in causing regression of LVH. Vasodilators, such as minoxidil and hydralazine, do not have an effect on regression, possibly because reflex tachycardia and stimulation of catecholamines and the renin-angiotensin system associated with these agents may negate the benefit of reduced afterload. There is some controversy regarding the ability of the angiotensin receptor blockers to reduce LVH. In some studies, these agents were associated with regression, whereas in others they were not. Whether targeting LVH as the primary treatment goal in hypertensive patients will have long-term benefits on outcome above and beyond simply reducing blood pressure is not clear.
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PMID:Case 3: A patient with systemic hypertension and left ventricular hypertrophy. 1072 68

Vascular hypertrophy occurs during chronic hypertension and contributes to the elevation of peripheral vascular resistance in hypertension. In this study, we examined whether acute pressure overloading of the vascular wall produces activation of mitogen-activated protein (MAP) kinases, enzymes believed to be involved in the pathway for cell proliferation, in isolated perfused rat aortae, and examined whether the mechanical overloading-induced MAP kinase activation is mediated via the vascular angiotensin system. Aortae were perfused with Tyrode solution. Increases in perfusion pressure caused a pressure-dependent increase in MAP kinase activity in endothelium-intact aortae and in endothelium-denuded aortae. The increase in MAP kinase activity induced by pressure loading was inhibited by the angiotensin receptor antagonist, losartan, the renin inhibitor, pepstatin A, and the angiotensin-converting enzyme inhibitor, captopril. Ca(2+) depletion and the Ca(2+) channel antagonist, nifedipine, did not affect the pressure loading-induced MAP kinase activation. The results of the present study suggest that pressure loading of the vascular wall per se can activate MAP kinases in the vasculature and that the MAP kinase activation is mediated at least partly via the vascular angiotensin system. It seems unlikely that the pressure loading-induced increase in MAP kinase activity is mainly mediated via increases in Ca(2+) influx in vascular cells.
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PMID:Angiotensin II mediates pressure loading-induced mitogen-activated protein kinase activation in isolated rat aorta. 1072 70

This article reviews the impressive amount of knowledge accumulated in the last few years on the angiotensin II AT2 subtype receptor. Although still elusive, a large body of experimental evidence strongly suggests that it may play an important role in the adaptive changes of the cardiovascular structures in response to pathological conditions such as myocardial infarction, congestive heart failure or hypertension. The most intriguing aspects of the biology of this receptor, however, appear to be: 1) the regulation of its transcription, which plays an important role in the expression of the protein in adults or in injured tissues; 2) its interaction or "cross-talk" with the predominant angiotensin II receptor, the AT1 subtype, or with the receptors of other growth factors or cytokines; and 3) its connections with the bradykinin/nitric oxide pathways. These aspects may be relevant for the therapeutical use of drugs which antagonize the renin-angiotensin system, such as angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, as well as for new therapeutic approaches to the treatment of cardiovascular diseases.
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PMID:Angiotensin II AT2 subtype receptors: an emerging target for cardiovascular therapy. 1073 Jun 8

It has been established that deoxycorticosterone acetate (DOCA)-salt hypertensive rats have an overactive brain angiotensin-system. The purpose of the present study was to identify the brain sites showing enhanced angiotensin-system activity responsible for the pathogenesis of hypertension in DOCA-salt hypertensive rats. The angiotensin receptor antagonist, losartan, was injected into brain ventricles or into tissues around the rostral parts of the third ventricle in conscious DOCA-salt hypertensive rats. Losartan (1 microg) injection into the lateral ventricle or into the rostral parts of the third ventricle produced a depressor response, whereas the agent did not affect blood pressure when injected into the caudal parts of the third ventricle or into the fourth ventricle. Losartan (0.1 microg) injection into the anterior hypothalamic preoptic area, anterior (AHA) produced a depressor response. Angiotensin II (0.1-1 ng) injection into the AHA produced a pressor response in sham-operated and DOCA-salt hypertensive rats, and the pressor response to angiotensin II (1 ng) was greater in DOCA-salt hypertensive rats than that in sham-operated rats. Release of angiotensin peptides in the AHA was greater in DOCA-salt hypertensive rats than that in sham-operated rats. These findings suggest that the angiotensin-system in the AHA is enhanced, and that this enhancement is involved in the maintenance of hypertension in DOCA-salt hypertensive rats. Both increased pressor reactivity to angiotensin II and increased release of angiotensin peptides in the AHA appear to be related to this enhancement of the angiotensin-system in DOCA-salt hypertensive rats.
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PMID:Blockade of angiotensin receptors in the anterior hypothalamic preoptic area lowers blood pressure in DOCA-salt hypertensive rats. 1077 Feb 57

A 67-year-old man with a one-and-a half-year history of Raynaud's phenomenon was admitted to our hospital for progressive dyspnea occurring over the previous two weeks. Physical examination revealed a blood pressure of 200/124 mmHg, and slightly tight and smooth skin of the fingers, hands and forearms. Laboratory evaluation included serum creatinine of 5.42 mg/dl, plasma renin activity > 20 ng/ml/hr, and antinuclear antibody with a titer of 1 : 1,280. Renal biopsy was performed and the histopathological findings showed that some glomeruli exhibited ischemic retraction with wrinkling of the basement membranes, and that one arteriole exhibited significant intimal hyperplasia with luminal stenosis. These findings were compatible with scleroderma renal crisis (SRC). On the 5th day, serum creatinine had risen to 9.16 mg/dl, and he required temporary hemodialysis therapy. After the administration of captopril was started, his blood pressure fell to 160/86 mmHg and serum creatinine was reduced to 5.12 mg/dl. On the 9th day, he exhibited skin eruptions, and captopril was discontinued accordingly and temocapril started. Because of continued eruptions, temocapril was replaced by losartan. His blood pressure was controlled easily and his serum creatinine level reduced steadily. One year after the start of losartan, serum creatinine was 2.25 mg/dl and blood pressure was 130/82 mmHg. SRC is a life-threatening manifestation of systemic sclerosis. In the late 1970s, angiotensin converting enzyme (ACE) inhibitor was introduced and has dramatically improved the outcome in SRC patients. As ACE inhibitors act mainly on hyperreninemic renal vasoconstrictive hypertension in SRC, we would expect losartan, a selective antagonist of angiotensin receptor subtype 1, to be interchangeable with ACE inhibitors in SRC. In 1997, Caskey and colleagues reported the failure of losartan to control hypertension in a patient of SRC, and the reason has remained unclear. We report here, a case of SRC whose blood pressure was controlled successfully and his renal failure reversed by the administration of losartan.
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PMID:[Successful use of angiotensin II receptor antagonist (losartan) in a patient with scleroderma renal crisis]. 1077 77

Spironolactone, a competitive aldosterone receptor antagonist (ARA), has traditionally been the treatment of first choice in idiopathic hyperaldosteronism (IHA) and for preoperative management of aldosterone producing adenoma (APA). Spironolactone is partially absorbed, is extensively metabolized mainly by the liver and its therapeutic properties are attributable to active metabolite canrenone. At therapeutic doses of 25 to 400 mg per day, spironolactone effectively controls blood pressure and hypokalemia in the majority of cases. Endocrine side effect are often associated and mainly consist of gynecomastia, decreased libido and impotence in man and menstrual irregularities in women. Canrenone and the K+ salt of canrenoate are also in clinical use: they avoid the formation of intermediate products with anti-androgenic and progestational actions, resulting in a decreased incidence of side effects. Furthermore, a relatively new selective ARA compound (eplerenone) with reduced affinity for androgen and progesterone receptors, is currently undergoing clinical trials. In essential hypertension aldosterone can contribute to hypertension and increases the incidence of myocardial hypertrophy and cardiovascular events. On the other hand, inhibition of Renin-Angiotensin-Aldosterone System (RAAS) is associated with a decrease in blood pressure, with a regression of left ventricular hypertrophy and a reduction of target organ damage. Thus, ARA have been proposed as complementary treatment associated to ACE inhibitors and angiotensin receptor antagonists. Aldosterone is also known to play an important role in pathophysiolgy of congestive heart failure (CHF). In vitro and in vivo evidences suggest that aldosterone promotes myocardial fibrosis. This effect reflects direct, extra-epithelial actions of aldosterone via cardiac MR which are counteracted by ARAs in animal models. The RAAS is chronically activated in CHF. Non potassium-sparing diuretics further stimulate the RAAS and cause hypokalemia. Thus, use of ARAs in CHF was first proposed to correct potassium and magnesium depletion. At present ARAs are indicated in the management of primary hyperaldosteronism, in oedematous conditions in patients with CHF, in cirrhosis of the liver accompanied by oedema and ascites, in essential hypertension and in hypokalemic states. Its indication as adjunctive therapy of heart failure is currently under investigation. In fact, it is well known that even high doses of ACE inhibitors may not completely suppress the RAAS; aldosterone 'escape' may occur through non angiotensin II dependent mechanisms. Addition of spironolactone to an ACE inhibitor causes marked diuresis and symptomatic improvement. During the last few years, the RALES study (Randomized Aldactone Evaluation Study) was organized to explore the efficacy of combination therapy with spironolactone and ACE inhibitor in patients with CHF, class III or IV NYHA. The study was stopped 18 months early because the results were so statistically and clinically significant that it would be unethical to continue the trial. It is reported a 30 percent decrease in mortality and hospitalisation for cardiac causes in spironolactone-treated group vs placebo group.
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PMID:Aldosterone antagonists in hypertension and heart failure. 1079 May 93

It is well known that essential hypertension evolves in most patients with "near normal" levels of plasma renin activity. However, these levels appear to be responsible for the high levels of arterial pressure because they are normalized by the administration of angiotensin II converting inhibitors or angiotensin receptor antagonist. In experimental animals, hypertension can be induced by the continuous intravenous infusion of small doses of angiotensin II that are not sufficient to evoke an immediate pressor response. However, this condition resembles the characteristics of essential hypertension because the high levels of blood pressure exist with normal plasma levels of angiotensin II. It is suggested that small amounts of angiotensin whose plasma levels are inappropriate for the existing size of extracellular volume stimulate oxidative stress which binds nitric oxide forming peroxynitrite. The latter compound oxidizes arachidonic acid producing isoprostaglandin F2alpha (an isoprostane) which is characterized by a strong antinatriuretic vasoconstrictor renal effect. In this chain of reactions the vasoconstrictor effects derived from oxygen quenching of nitric oxide and increased isoprostane synthesis could explain how hypertension is maintained with normal plasma levels of renin.
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PMID:Oxidative stress may explain how hypertension is maintained by normal levels of angiotensin II. 1082 93

An overactive brain renin-angiotensin system is one of the factors contributing to the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). We examined brain sites where enhanced activity of an angiotensin system is responsible for the pathogenesis of hypertension in SHR. The angiotensin receptor antagonist, losartan was injected into tissues around rostral parts of the third ventricle in conscious rats. Losartan (0.22 nmol) injected into the anterior hypothalamic area, anterior (AHA) produced a depressor response in SHR but not in Wistar Kyoto rats (WKY). Angiotensin II (0.091-0.91 pmol) injected into the AHA produced a pressor response in both WKY and SHR, and the pressor response to angiotensin II was greater in SHR than that of WKY. Carbachol (3 pmol) injected into the AHA also produced a pressor response in WKY and SHR, and the pressor response to carbachol was almost the same in both strains of rats. Release of angiotensin peptides in the AHA was greater in SHR than that of WKY. These findings suggest that an angiotensin system in the AHA is enhanced and this enhancement of angiotensin system is involved in the maintenance of hypertension in SHR. Both increased pressor reactivity to angiotensin II and increased release of angiotensin peptides in the AHA appear to be related to this enhancement of angiotensin system in SHR.
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PMID:An angiotensin system in the anterior hypothalamic area anterior is involved in the maintenance of hypertension in spontaneously hypertensive rats. 1085 27

More women than men eventually develop hypertension in the United States due to their higher numbers and longer longevity. The white coat hypertension is also more common in women. Alcohol, obesity and oral contraceptives are important causes of rise in blood pressure among women. On the other hand, hormone replacement therapy may decrease cardiovascular mortality in the postmenopausal woman. Women with left ventricular hypertrophy are at a greater risk of death than men. Fibromuscular hyperplasia and primary aldosteronism are more common as causes of secondary hypertension in women. Nonpharmacologic therapy, such as weight reduction, exercise, salt and alcohol reduction, should always be tried prior to medical treatment of hypertension and are very useful adjunctive measures in controlling hypertension. ACE inhibitors and angiotensin receptor blockers are contraindicated in pregnancy and should be avoided in women with childbearing potential. Hypertension remains a major public health problem among black women. Although the antihypertensive drug therapy seems to benefit white women the least, proportionately more of them comply with their antihypertensive therapy. Hypertension is the most common chronic medical condition requiring visits to the physicians, as well as prescription medications, in the United States. The epidemiology, clinical course, response to treatment and ultimate outcome of essential hypertension may vary with gender. More women than men eventually develop hypertension in the US due to their higher numbers and longer longevity.
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PMID:Hypertension in women. 1092 86


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