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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Considerable evidence now indicates that a separate and distinct renin-angiotensin system (RAS) is present within the brain. The necessary precursors and enzymes required for the formation and degradation of the biologically active forms of angiotensins have been identified in brain tissues as have angiotensin binding sites. Although this brain RAS appears to be regulated independently from the peripheral RAS, circulating angiotensins do exert a portion of their actions via stimulation of brain angiotensin receptors located in circumventricular organs. These circumventricular organs are located in the proximity of brain ventricles, are richly vascularized and possess a reduced blood-brain barrier thus permitting accessibility by peptides. In this way the brain RAS interacts with other neurotransmitter and neuromodulator systems and contributes to the regulation of blood pressure, body fluid homeostasis, cyclicity of reproductive hormones and sexual behavior, and perhaps plays a role in other functions such as memory acquisition and recall, sensory acuity including pain perception and exploratory behavior. An overactive brain RAS has been identified as one of the factors contributing to the pathogenesis and maintenance of hypertension in the spontaneously hypertensive rat (SHR) model of human essential hypertension. Oral treatment with angiotensin-converting enzyme inhibitors, which interfere with the formation of angiotensin II, prevents the development of hypertension in young SHR by acting, at least in part, upon the brain RAS. Delivery of converting enzyme inhibitors or specific angiotensin receptor antagonists into the brain significantly reduces blood pressure in adult SHR. Thus, if the SHR is an appropriate model of human essential hypertension (there is controversy concerning its usefulness), the potential contribution of the brain RAS to this dysfunction must be considered during the development of future antihypertensive compounds.
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PMID:Regulatory role of brain angiotensins in the control of physiological and behavioral responses. 136 94

Activation of the renin-angiotensin system by sodium deficiency is associated with reciprocal changes in the expression of angiotensin II receptors in adrenal glomerulosa and vascular smooth muscle cells. The effects of dietary sodium changes on the expression of brain angiotensin receptor subtype 1 (AT1) mRNAs were examined in rats maintained on normal, low, and high sodium intake for 3 weeks. Plasma aldosterone and renin activity were elevated in rats maintained on a low salt diet compared with normal rats and were reduced in rats maintained on a high salt diet. These results are consistent with previous findings on the effects of altered dietary sodium on the renin-angiotensin system. The expression of AT1A and AT1B receptor subtype mRNAs was determined by quantitative reverse transcriptase-polymerase chain reaction during changes in sodium intake. The results revealed that sodium deprivation enhanced the expression of AT1B receptors in decorticated brains by 164% compared with high sodium intake. Conversely, high sodium diet increased the expression of AT1A receptors by 155% in the brain compared with low sodium intake. These data suggest that AT1A and AT1B receptors play reciprocal roles in central mechanisms for the control of fluid homeostasis. Further analysis of the molecular biology of angiotensin II receptor regulation in the brain may provide new insights into the interplay between the renin-angiotensin system and blood pressure regulation and also into the role of angiotensin II in the pathogenesis of essential hypertension.
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PMID:Regulation of angiotensin II receptors in rat brain during dietary sodium changes. 750 98

The brain GABAergic system was previously shown to influence blood pressure (BP) maintenance in rats which may in part be accomplished by disruption of the central renin-angiotensin system (RAS). We examined the potential role of GABA in sustaining the high BP exhibited by the spontaneously hypertensive rat (SHR) model of human essential hypertension. Intracerebroventricular (i.c.v.) infusion of GABA produced decreases in BP in members of three rat strains, including Wistar-Kyoto (WKY) and Sprague-Dawley normotensive controls and SHR. The SHR were significantly more sensitive to GABA than the normotensive strains. Next, the GABA receptor antagonist bicuculline (BMI) was infused i.c.v. and produced increases in BP in members of each strain. Finally, i.c.v. pretreatment with the specific angiotensin receptor antagonist [Sar1, Thr8]AII (sarthran), blocked subsequent GABA-induced decreases in BP in members of all three strains, and there was a trend toward sarthran attenuation of BMI-induced increases in BP. These results encourage the hypothesis that the hypotensive effects produced by central application of GABA are mediated by the brain angiotensin system.
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PMID:GABA and bicuculline-induced blood pressure changes in spontaneously hypertensive rats. 767 72

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

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

Microalbuminuria (MA) is defined as persistent elevation of albumin in the urine, of 30-300 mg/day (20-200 microg/min). These values are less than the values detected by routine urine dipstick testing, which does not become positive until protein excretion exceeds 300-500 mg/day. Use of the albumin-to-creatinine ratio is recommended as the preferred screening strategy for all diabetic patients. MA is measured in spot morning urine obtained from the patient in the office and sent for measurement of both albumin and creatinine. A value above 0.03 mg/mg suggests that albumin excretion is above 30 mg/day and therefore MA is present. MA should be checked annually in everyone, and every 6 months within the first year of treatment to assess the impact in patients started on antihypertensive therapy. MA is an established risk factor for renal disease progression in type 1 diabetes and its presence is the earliest clinical sign of diabetic nephropathy. In addition, a number of studies suggest that MA is an important risk factor for cardiovascular disease and defines a group at high risk for early cardiovascular mortality in both type 2 diabetes and essential hypertension. MA also signifies abnormal vascular permeability and the presence of atherosclerosis. Among nondiabetic patients with essential hypertension, MA is associated with higher blood pressures, increased serum total cholesterol, and reduced serum high-density lipoprotein cholesterol. Thus, taken together these data support the concept that the presence of MA is the kidney's notice to the physician/patient that there is a problem with the vasculature. MA can be reduced, and progression to overt proteinuria prevented, by aggressive blood pressure reduction. The National Kidney Foundation recommends that blood pressure levels be maintained at or below 130/80 mm Hg in anyone with diabetes or renal disease. This should be accomplished with antihypertensive agents that prevent the rise in MA and hence prevent development of proteinuria. Such agents are angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and, to a lesser extent, Beta blockers, non-dihydropyridine calcium antagonists, and diuretics. In summary, the presence of MA is a marker of endothelial dysfunction and a harbinger of markedly enhanced cardiovascular risk. All patients with diabetes and/or hypertension should be screened for the presence of microalbuminuria with use of spot morning urine. To maximize prevention of MA development, the following goals should be instituted: 1) blood pressure should be maintained at less than 130/80 mm Hg and a low-salt, moderate-potassium diet instituted; 2) in diabetics, HbA1c should be kept at less than 7%; 3) in obese patients, a weight loss program should be implemented, with a goal BMI of less than 30; and 4) the physician and patient, working together, should maintain low-density lipoprotein cholesterol at less than 120 mg/dL, and less than 100 mg/dL if diabetes is present. (c)2001 by Le Jacq Communications, Inc.
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PMID:Microalbuminuria: what is it? Why is it important? What should be done about it? 1141 91

The objective of this study was to evaluate the long-term effects of enalapril, an angiotensin-converting enzyme inhibitor, and losartan, an angiotensin type 1 receptor antagonist, on the proliferation of peripheral blood mononuclear cells (PBMC) in patients with essential hypertension. Nine patients with a sitting diastolic blood pressure of > 95 mmHg and < 105 mmHg at the end of a 4-week placebo run-in period entered the double-blind phase of the study, which consisted of three 6-week periods during which patients were treated with placebo, enalapril (20 mg o.d.) or losartan (50 mg o.d.) The de novo synthesis of DNA, RNA and protein in PBMC was measured by [3H]-thymidine, [3H]-uridine or [3H]-leucine incorporation, respectively. Neither enalapril nor losartan affected the proliferation of PBMC measured as de novo synthesis of DNA, RNA and protein. Our data show that proliferation was not affected during angiotensin-converting enzyme inhibition with enalapril and angiotensin receptor type 1 antagonism with losartan.
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PMID:Long-term treatment with enalapril or losartan does not show antiproliferative effects in peripheral blood mononuclear cells. 1152 15

We conducted a systematic review of randomized, controlled, monotherapy trials since 1990 of oral antihypertensive agents in patients with essential hypertension. Our objective was to quantify the frequency of discontinuation of antihypertensive agents due to adverse events from a meta-analysis of the studies. A total of 190 studies met inclusion criteria. The highest frequency of discontinuations due to adverse events (DAEs) occurred with calcium channel blockers (6.7%) and alpha-adrenergic blockers (6.0%); the lowest with diuretics and angiotensin receptor blockers (each 3.1%). Only in calcium channel blocker studies was the frequency of DAEs greater in treated patients than in patients receiving placebo, but the difference was not significant. This systematic review suggests that the frequency of DAEs in monotherapy antihypertensive trials varies across drug classes and should be considered when choosing drugs for patients with essential hypertension.
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PMID:Discontinuation of antihypertensive drugs due to adverse events: a systematic review and meta-analysis. 1171

These 25 lessons 1) review the roles of plasma renin levels for causing malignant and most essential hypertension and their related vascular injuries (heart attack, heart failure, kidney failure and stroke); 2) review how antihypertensive anti-R drugs that block renin activity (beta blockers, the first converting enzyme inhibitor from venom, and the first angiotensin receptor blocker) were used to reveal plasma renin involvement in the hypertension of medium and high renin patients and to show; 3) that the 30% with low renin essential hypertension do not respond to R drugs, are not prone to heart attack or stroke, and BP is corrected instead by the natriuretic anti-V drugs (diuretics, spironolactone, CCB, alpha blockers); 4) thus, all hypertensives can be divided into R patients who have too much renin vasoconstriction or V patients who instead have predominant sodium-volume mediation. Furthermore, all antihypertensive drug classes can be divided into R drugs that block the renin factor, or V drugs that reduce body sodium volume; 5) these findings document our conception of two biochemically and physiologically different final factors that sustain all BP in which the sodium-volume factor continuously sustains cardiac output and flow while plasma renin-angiotensin sets total peripheral resistance (TPR), which, within the Poiseuille Equation (BP = cardiac output [CO] x TPR) describes our [Na+-volume x renin-angiotensin vasoconstriction] model that supports all normotension or hypertension; 6) in this light, we designed a visit-by-visit method for treating untreated hypertensives using the ambient plasma renin level and BP responses to guide primary drug therapy against either the V or R factor; and 7) for also correcting nonresponders receiving multiple drugs where renin testing correctly guides addition or subtraction of drugs depending on whether the test indicates unresponsiveness due to a reactive sodium-volume excess, or to lack of effectiveness of an R drug in a V patient or of a V drug in an R patient, or from large reactive increases in renin that override the R drug, calling for strengthening the R and/or removing V drugs. This objective, biochemically based method results in effective longterm BP control of nearly all patients using fewer, but the correct drug(s) for each individual.
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PMID:Abstract, closing summary, and table of contents for Laragh's 25 lessons in pathophysiology and 12 clinical pearls for treating hypertension. 1177 22


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