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

Hypertension is prevalent world-wide, and it affects over 50 million individuals in the United States alone. African Americans (blacks) have a high prevalence of hypertension, develop it at an earlier age, and suffer excessively from severe or malignant hypertension. They also have a high prevalence of target organ damage attributable to hypertension, including left ventricular hypertrophy, stroke, end-stage renal disease (ESRD) and coronary artery disease. Hypertensive nephrosclerosis is particularly more prevalent in blacks compared to whites, and there is evidence that factors in addition to elevated blood pressure contribute to its pathogenesis. Transforming growth factor-beta 1 (TGF-beta1) is a fibrogenic cytokine that has been implicated in the development and progression of experimental and human renal diseases. We have demonstrated that blacks with ESRD have higher circulating levels of TGF-beta1 protein compared to whites with ESRD. We have also found that hyperexpression of TGF-beta1 is more frequent in blacks with hypertension than in whites. We propose that TGF-beta1 hyperexpression may be an important mediator of hypertension and hypertensive nephrosclerosis. We hypothesize also that the increased frequency of TGF-beta1 hyperexpression may contribute to the excess burden of ESRD in blacks. Based on our hypotheses, and the observations that angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists reduce angiotensin II-mediated stimulation of TGF-beta1 production, we propose that treatment with these agents might be efficacious in preventing or slowing the progression of target organ damage in hypertensive blacks.
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PMID:Hypertension-induced organ damage in African Americans: transforming growth factor-beta(1) excess as a mechanism for increased prevalence. 1098 Nov 47

Vascular changes associated with elevated blood pressure may precede the clinical diagnosis of hypertension. Even after the diagnosis is made, associated coronary heart disease and renal disease continue to progress, despite adequate blood pressure control. Early treatment of blood pressure may reduce the incidence of clinical hypertension and reduce the long-term consequences of hypertension. Animal studies have shown that early blood pressure lowering, through blockade of the renin-angiotensin system, prevents long-term hypertension. Prevention is an important goal in the treatment of hypertension. Our best attempts to prevent hypertension use nonpharmacologic methods of diet and exercise. These methods are fraught with difficulties of implementation and compliance that limit their success. Finding novel approaches to prevent hypertension may have a major impact on the incidence of hypertension. We are investigating the effect of 2 years of treatment with an angiotensin receptor blocker (candesartan cilexitil) compared with placebo, followed by 2 years of follow-up, on the incidence of hypertension in patients with high-normal blood pressure. Incidence of hypertension after discontinuation of active treatment will be compared with the incidence in the placebo group. There will be 1000 patients enrolled in the study, which will be completed in 2004.
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PMID:Prehypertension: a possible target for antihypertensive medication. 1098 Nov 70

Regulation mechanisms of the activity of vascular mitogen-activated protein (MAP) kinases, enzymes believed to be involved in the pathway for cell proliferation, may be altered in hypertension. To examine whether vascular MAP kinase activation mechanisms are altered in hypertension, we measured the activity of MAP kinases in rat aorta strips from spontaneously hypertensive rats (SHR) and from deoxycorticosterone acetate (DOCA)-salt hypertensive rats, and examined whether vascular angiotensin and endothelin systems are responsible for the alteration of MAP kinase activation in these hypertensive models. Endothelium-denuded aorta strips were incubated at 37 degrees C in medium. MAP kinase activity after incubation was increased in rat aorta strips. The MAP kinase activation was greater in 9- and 15-week-old SHR aorta strips than in age-matched Wistar Kyoto rats (WKY) aorta strips. Similarly, MAP kinase activation was enhanced in aorta strips from DOCA-salt hypertensive rats. In aorta strips from these kinds of rats, the angiotensin receptor antagonist, losartan, and the endothelin receptor antagonist, cyclo (D-alpha-aspartyl-L-prolyl-D-valyl-L-leucyl-D-tryptophyl) (BQ123), inhibited the MAP kinase activation. The losartan-induced, but not BQ123-induced, inhibition of MAP kinase activation was enhanced in 15-week-old SHR aorta strips, whereas the BQ123-induced, but not losartan-induced, inhibition of MAP kinase activation was enhanced in DOCA-salt hypertensive rat aorta strips. Angiotensin II-induced MAP kinase activation was enhanced in 15-week-old SHR aorta strips, whereas it was depressed in DOCA-salt hypertensive rat aorta strips. These results indicate that MAP kinase activation function is enhanced in aorta strips from both kinds of hypertensive rats. It appears that the enhancement of MAP kinase activation results partly from enhanced vascular angiotensin system in SHR and from enhanced vascular endothelin system in DOCA-salt hypertensive rats.
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PMID:Different activation of vascular mitogen-activated protein kinases in spontaneously and DOCA-salt hypertensive rats. 1098 39

The renin-angiotensin-aldosterone system actively participates in the derangement of renal function since the early stages of heart failure (HF). A diminished capacity to excrete sodium secondary to increased proximal tubular re-absorption and loss of the renal functional reserve are the two most relevant initial alterations of renal function in which angiotensin II has been proven to act directly. Meanwhile, the octapeptide contributes to maintain glomerular filtration rate (GFR) within normal limits through efferent arteriole vasoconstriction. Administration of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor antagonists (ARA) may thus be accompanied by a functional fall in that parameter. Advanced age, higher initial serum creatinine, history of hypertension, diabetes and atrial fibrillation predict the onset of GFR impairment associated with blockade of the renin-angiotensin system. Concomitant administration of betablockers may help to protect renal function, and preliminary data indicate that the combination of ACEi and ARA is not accompanied by a higher renal risk. The good prognostic effects of aldosterone antagonists in HF does not seem to be related to intrarenal effects of these compounds with the exception of preventing potassium loss and hypokalemia. The systematic therapeutic use of drug(s) provided with beneficial renal effects, to treat arterial hypertension or myocardial ischemia, may contribute to delay of, or prevent the development of HF.
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PMID:Renal implications of the renin-angiotensin-aldosterone system blockade in heart failure. 1108 65

Physicians must aggressively treat heart failure in the early stages to prevent disease progression and improve survival. Early treatment implies early diagnosis of left ventricular (LV) dysfunction, before the onset of symptoms. Patients with risk factors for the development of heart failure, especially coronary disease or hypertension, should undergo echocardiography to evaluate LV function. Patients with LV systolic dysfunction should be further evaluated to determine the type of cardiac dysfunction, uncover correctable etiologic factors, determine prognosis, and guide treatment. Angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blocking drugs improve survival and are integral to the treatment plan. Physicians should prescribe an ACE inhibitor as initial therapy for all patients with LV systolic dysfunction unless there are specific contraindications. The combination of hydralazine and isosorbide dinitrate is an acceptable alternative therapy for patients who cannot take ACE inhibitors. Diuretics should be used if there are signs or symptoms of volume overload. Beta-adrenergic blocking drugs should be added to therapy in stable patients with mild to moderate heart failure after optimal treatment with ACE inhibitors, diuretics, or other vasodilators. Digoxin should be used routinely in patients with severe heart failure and should be added to therapy in patients with mild to moderate heart failure who remain symptomatic despite optimal doses of ACE inhibitors and diuretics. Spironolactone should be added, but electrolytes should be closely monitored. Warfarin anticoagulation should be considered in patients with a left ventricular ejection fraction (LVEF) of 35% or less. Until survival data exist, angiotensin receptor blockers (ARBs) should not be used as initial therapy or as sole therapy but can be used for ACE-intolerant patients or can be added to standard heart failure therapy. Outpatient use of intravenous inotropic therapy should be avoided. Patients with severe heart failure should have peak oxygen consumption measured to quantify functional impairment, determine prognosis, and identify the need for advanced heart failure therapy. Patients who remain symptomatic while receiving optimal standard therapy should be referred early to a specialized heart failure center.
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PMID:Chronic Heart Failure. 1109 88

Angiotensin-converting enzyme (ACE) inhibitors appear to possess unique cardioprotective benefits, even when used in patients without high blood pressure or left ventricular dysfunction (the traditional indications for ACE inhibitor therapy). The ACE inhibitors improve endothelial function and regress both left ventricular hypertrophy and arterial mass better than other antihypertensive agents that lower blood pressure equally as well. These agents promote collateral vessel development and improve prognosis in patients who have had a coronary revascularization procedure (i.e., percutaneous transluminal coronary angioplasty and coronary artery bypass graft surgery). Insulin resistance, present not only in type 2 diabetes but also commonly in patients with hypertension or coronary artery disease, or both, sensitizes the vasculature to the trophic effects of angiotensin II and aldosterone. This may partly explain the improvement in prognosis noted when patients who have atherosclerosis or diabetes are treated with an ACE inhibitor. Therapy with ACE inhibitors has also been shown, in two large, randomized trials, to reduce the incidence of new-onset type 2 diabetes through largely unknown mechanisms. The ACE inhibitors are safe, well tolerated and affordable medications. The data suggest that most people with atherosclerosis should be considered candidates for ACE inhibitor therapy, unless they are intolerant to the medication, or have systolic blood pressures consistently <100 mm Hg. Patients who show evidence of insulin resistance (with or without overt type 2 diabetes) should also be considered as candidates for prophylactic ACE inhibitor therapy. Although angiotensin receptor blockers should not be considered equivalent to ACE inhibitors for this indication, they may be a reasonable alternative for patients intolerant of ACE inhibitors.
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PMID:Should an angiotensin-converting enzyme inhibitor be standard therapy for patients with atherosclerotic disease? 1115 22

Hypertension plays a critical role in causing a high rate of cardiovascular events in patients with diabetes mellitus. Large trials show that lowering blood pressure in the patient with diabetes who has hypertension has profoundly favorable effects. This review discusses recent trials to answer the question of how low patients' blood pressure should go and which agents should be used to achieve this goal. The National Institutes of Health's guidelines, published in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, call for a blood pressure goal of <130/85 mmHg in patients with diabetes. Based on data from the recent trials, an even lower blood pressure of <130/80 mmHg in patients with diabetes and hypertension appears to be appropriate. Observational studies show that the lowest cardiovascular event rate is observed in patients with diabetes whose systolic blood pressure is <120 mmHg. Thus, goal blood pressure in patients with diabetes who have hypertension may need to be revised lower, to <120/80 mmHg. In patients with overt proteinuria of 1 g/d or more, mean arterial pressure of <92 mmHg is recommended. Available evidence justifies the use of angiotensin-converting enzyme (ACE) inhibitors as first-line agents and angiotensin receptor blockers in those patients who are intolerant to ACE inhibitors. Because the blood pressure goal is lower in patients with diabetes who are hypertensive, these patients require the use of multiple agents. Diuretics or long-acting calcium channel blockers are logical second choices because of their synergistic blood pressure reduction effect observed with ACE inhibitors. Alpha-blockers should be used with caution, however. In patients with renal disease, loop diuretics may be required to reduce sodium and volume overload and to improve blood pressure control.
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PMID:Treatment of hypertension in patients with diabetes: lessons from recent trials. 1117 14

The renin angiotensin system was demonstrated to play a significant role in the genesis of hypertension and regulation of vascular tone over 100 years ago. The early investigations were subsequently expanded to implicate the renin angiotensin system in a variety of physiologic processes that may play a significant role in the initiation and progression of atherosclerosis. The renin angiotensin system modulates vascular structure and left ventricular hypertrophy via a number of trophic effects. Elevated levels of angiotensin II are associated with the generation of oxidative stress, and may thus play a significant role in the earliest phases of atherosclerosis. The role inflammation plays in atherosclerosis is amplified by the renin angiotensin system via the effects on adhesion molecules, growth factors, and chemoattractant molecules, which modulate the migration of inflammatory cells into the subendothelial space. The effects of angiotensin II, which may be at least partially genetically mediated, have been implicated in epidemiologic and clinical studies as a risk factor for the development of atherosclerosis. This review centers on the potential role that the renin angiotensin system plays as a risk factor for the development of atherosclerosis, and the role of converting enzyme inhibition or angiotensin receptor blockade as a mechanism to decrease the initiation, progression, and clinical consequences of the atherosclerotic process.
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PMID:The renin angiotensin system as a risk factor for coronary artery disease. 1117 55

This is a personal historical account relating the events that led to the first application of angiotensin inhibition (either by ACE inhibitors or by angiotensin receptor blockade) to the investigation of the pathogenesis and treatment of hypertension, ischemic heart disease, and heart failure. Included are animal experiments, clinical observations, and the earliest clinical experimental studies that helped define some of the detrimental effects of angiotensin II and the beneficial hemodynamic results of its inhibition, which have been subsequently corroborated and amplified by large randomized outcome trials.
Hypertension 2001 Feb
PMID:Role of angiotensin and its inhibition in hypertension, ischemic heart disease, and heart failure. 1123 Feb 97

The primary goal of antihypertensive therapy is to restore blood pressure to normal levels and to prevent the complications associated with hypertension. In order to maximize these goals by improving patient compliance, clinical researchers have focused on developing antihypertensive agents that can be given once daily. These agents provide many advantages over multiple-dose daily therapies, but it should not be assumed that they are all equivalent in providing adequate blood pressure control over the full 24-h dosing interval. Ambulatory blood pressure monitoring has uncovered important differences in commonly used once-daily therapies and has provided additional insights into the cardiovascular risks associated with high blood pressure loads and blood pressure variability. In addition to ambulatory blood pressure monitoring data, the calculated trough:peak ratio provides useful information on an agent's ability to provide smooth and consistent blood pressure control. Using such assessments, it has been found that agents with a trough:peak ratio > or = 0.50 are better able to control blood pressure over the full 24h while maintaining natural circadian patterns. Ambulatory blood pressure monitoring studies assessing a recently introduced class of antihypertensive drugs, the angiotensin receptor blockers, have demonstrated 24-h efficacy with once-daily dosing, particularly with the newer agents.
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PMID:The importance of 24-h blood pressure control. 1124 55


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