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

Antihypertensive therapy has been used for almost 35 years to reduce blood pressure and prevent morbidity and mortality related to the hypertensive state. Malignant, severe, and moderate hypertension have all been shown to be worthy of drug treatment, but controversy remains as to the degree of benefit that is achievable by treating milder hypertension. A variety of clinical trials have demonstrated that antihypertensive therapy reduces the incidence of stroke, congestive heart failure, and left ventricular hypertrophy and the progression in severity of hypertension. The benefits with respect to prevention of coronary heart disease (CHD) have been much less impressive. Thiazide diuretics have been the base therapy for the bulk of the hypertensive subjects studied to date who have not demonstrated reduced incidence of CHD. Therapy with beta-blockers has the potential for reducing CHD, but an analysis of four studies finds only two with positive results. On the other hand, since that study found reduced total mortality as well as CHD compared with thiazide diuretic, its findings cannot be ignored. Other questions deserving further investigation include how other antihypertensive therapies compare with respect to the risk reduction found with thiazide diuretics and beta-blockers, the optimal posttreatment blood pressure, whether persons with mild hypertension benefit from therapy, whether women should be treated differently, and whether atherosclerosis may be affected by specific antihypertensive therapies.
Hypertension 1991 Sep
PMID:Are some antihypertensive therapies more efficacious than others in preventing complications and prolonging life? 167 54

The evaluation and treatment of hypertension in the African-American patient with an elevated blood pressure presents a diagnostic challenge. We are less able to rely on young age and resistance to treatment as indications for more extensive evaluation of secondary causes of hypertension; thus, greater reliance on history, physical examination, and clinical judgment is required if we are to identify potentially treatable causes. The treatment of hypertension in the African-American patient also presents a therapeutic challenge. Thiazide diuretics remain the drugs of first choice for treating hypertension in the African-American hypertensive. The calcium channel blockers (CCBs) are attractive alternatives to thiazides in patients uncontrolled by or intolerant of thiazides or who have specific indications for these agents (eg, angina, severe diastolic dysfunction). Beta-blockers should not be denied to African-American hypertensives if indications for their use exist. Although beta-blockers may be less effective as monotherapy, 50% of African-American hypertensives can be so controlled. Resistance to beta-blockers may be eliminated by administering them with a diuretic. The angiotensin converting enzyme inhibitors (ACEIs), like CCBs, are well tolerated, but also lack long-term primary prevention data. As is the case with beta-blockers, ACEIs are less effective in African-American hypertensives when used as monotherapy. ACEIs have particular value in therapy for African-American hypertensives with concomitant congestive heart failure and may protect against progression of diabetic nephropathy. Finally, all hypertensives, especially African-American hypertensives, should have access to treatment prior to the development of end organ damage. The cost of early intervention is minimal compared with the economic consequences of neglect.
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PMID:Hypertension in African Americans: evaluation and treatment issues. 168 47

Kidney disease is a primary cause of morbidity and mortality in diabetic patients. Factors that predetermine development of nephropathy remain unknown. Poor glycemic control, insulin requirement, duration of diabetes and family history of hypertension appear to be associated with an increased risk. Arterial hypertension, which is twice as common in diabetic patients as in the normal population, accelerates the progression of diabetic nephropathy. The pathophysiologic mechanisms responsible for hypertension appear to be different in IDDM and NIDDM. In IDDM, hypertension occurs usually as a consequence of diabetic renal disease. Conversely, the pathogenesis in NIDDM appears to be multifactorial. In either condition, aggressive blood pressure control is the single most important intervention proven to retard the progression of nephropathy. A stepped-care approach similar to that for essential hypertension with slight modifications is indicated in the treatment of the hypertensive diabetic patient with nephropathy. Nonpharmacological therapy, including dietary protein restriction, should be used as first step. Selection of the ideal antihypertensive must be based not only on efficacy but also on its side effect profile. Angiotensin converting enzyme inhibitors and calcium antagonists have a low incidence of side effects and do not induce metabolic disturbances. Therefore, they are the agents of choice for patients who do not respond to nonpharmacological therapy alone. Thiazide diuretics and beta-blockers should be used as first line therapy only for specific indications. Antihypertensive therapy combined with good glycemic control and dietary protein restriction constitute the standard of care for diabetic patients with hypertension and renal disease.
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PMID:Hypertension and kidney disease of diabetes mellitus. 176 55

Several studies have shown that antihypertensive drugs therapy could reduce morbidity and mortality of hypertension related complication such as stroke, congestive heart failure and renal failure, but there was no significant reduction of coronary heart disease. The benefit of the treatment on morbidity and mortality may be counterbalanced by adversed metabolic effects of long-term therapy. The purpose of this study is to evaluate the blood pressure-lowering and adverse metabolic effects of chlorothiazide and propranolol monotherapy. A double-blind, cross-over design clinical trial was performed for 42 cases (22 males and 20 females) with the mean age of 52 (from 30 to 59 years old). After 2 weeks run-in period, the patients were assigned to group A and B with age and sex stratification. Chlorothiazide and propranolol were given for 12 weeks in alternative with 2 weeks placebo washout period. Our studies have shown that, chlorothiazide and propranolol could reduce both systolic and diastolic blood pressure significantly. But they also associated with adverse metabolic effects. Serum uric acid and triglyceride increased and decreased the concentration of high density lipoprotein cholesterol (HDL-C). Those changes could counterbalance the benefit of blood pressure-lowering effect of antihypertension. Carefully monitoring the adverse metabolic effects closely is necessary in therapy with these drugs.
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PMID:[Metabolic effects of chlorothiazide and propranolol on essential hypertension--a double-blind, cross-over design clinical trial]. 184 31

When combining a beta blocker with a diuretic in patients with hypertension, consideration should be given to the potential advantages of intrinsic sympathomimetic activity (ISA). During long-term administration of a beta blocker without ISA, total peripheral resistance stabilizes at or slightly above the pretreatment level. Since cardiac output is decreased, blood pressure falls. Thus, beta blockers without ISA may exacerbate the underlying haemodynamic abnormality of long-standing hypertension, increased systemic resistance. In contrast, the reduction in pressure which occurs with a beta blocker possessing a high degree of ISA, such as pindolol, is associated with a reduction in total peripheral resistance and little change in cardiac output. Thiazide diuretics and most beta blockers without ISA also have an adverse impact on the blood lipid profile, potentially increasing cardiovascular risk. With the exception of oxprenolol, monotherapy with beta blockers which possess ISA have generally had no adverse blood lipid changes. Indeed, pindolol has been shown to increase HDL-cholesterol and to reduce the ratio of total cholesterol to HDL-cholesterol. Pindolol administered in combination with several diuretics has not increased the adverse lipid effects of these agents and, in some studies, evidence suggests that pindolol may counteract some or all of these changes. The clinical significance of these differences between beta blockers with and without ISA remains uncertain. Nevertheless, the potential haemodynamic and metabolic benefit of agents with ISA mandate that they receive careful consideration when selecting a beta blocker to administer with a diuretic.
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PMID:Potential benefit of combination therapy with diuretics and beta blockers having intrinsic sympathomimetic activity. 197 64

It is generally agreed that moderate and severe hypertension in the elderly should be treated, but it is not clear which drug or drugs are most appropriate. Thiazide diuretics are inexpensive and effective, but they are associated with metabolic side effects that are becoming less acceptable as newer agents become available. Beta blockers are effective, but can be associated with central nervous system side effects and are often contraindicated by coexisting disease. Recently, attention has been focused on the newer agents, including calcium antagonists and angiotensin-converting enzyme inhibitors. The advantage of calcium antagonists is that they do not produce metabolic side effects. However, they are expensive and may cause vasodilatory side effects. The angiotensin-converting enzyme inhibitors are effective and relatively free of side effects and may be particularly useful for elderly hypertensive patients with congestive heart failure.
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PMID:Choice of drug treatment for elderly hypertensive patients. 200 57

Thiazide diuretics, which are often prescribed to treat mild to moderate hypertension, commonly cause an increase in urinary zinc (Zn) excretion. Metabolic interrelationships between Zn and copper (Cu) are known to exist; consequently, Zn might influence Cu levels. This study aims to determine whether or not Cu and Zn levels in hypertensive patients were influenced by treatment with clopamide, a thiazide diuretic. Eight male patients, aged 36-59 and with an average supine diastolic pressure of 95-115 mm Hg, were treated with single daily doses of clopamide 5 mg as monotherapy for 16 weeks. Plasma, erythrocyte (RBC), and mononuclear leukocyte (WBC) levels of Cu and Zn were determined immediately before therapy (week 0) and again at weeks 8 and 16. There was a significant fall in Cu in mononuclear WBCs from 13.25 (SEM = 0.86) to 1.9 fg/cell (SEM = 0.56) (p less than 0.001) and an increase in Zn from 33.87 (SEM = 3.7) to 70.8 fg/cell (SEM = 11.7) (p less than 0.001), with no change in either cell count or measurable cell volume. Plasma Cu levels increased significantly (p less than 0.001), but the Zn levels decreased only slightly (p less than 0.03). Changes in RBC Cu levels during the treatment period were not significantly altered (p less than 0.1). Zn levels in RBCs were significantly (p less than 0.04) lower. It is concluded that treatment with clopamide may induce some changes in Cu and Zn levels in normal hypertensives, particularly in WBCs. Further investigation is needed to determine the extent of this influence.
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PMID:Effect of clopamide, a thiazide diuretic, on copper and zinc levels in hypertensive patients. 201 May 78

Indapamide, a nonthiazide diuretic, exhibits direct vasodilator action as well as natriuretic and diuretic effects. Although calcium antagonist-like activity has been addressed so far, the mechanisms for vasodilator effect are still uncertain. To understand the wide range of indapamide actions, we examined the effects of indapamide on the vascular eicosanoid generation and investigated its mechanisms by using rat vascular smooth muscle cells in culture. Indapamide uniquely increased the prostacyclin generation in the vascular smooth muscle cells in a dose-dependent manner, whereas it did not affect the vasoconstrictor thromboxane A2. Thiazide diuretics lowered the prostacyclin generation, while nonthiazide derivatives did not affect the biosynthesis. Enzymatic analysis revealed that indapamide affected neither [14C]arachidonate liberation nor prostacyclin synthase of the smooth muscle cells. Indapamide eliminated a stable free radical in a cell-free system, lowered the formation of malondialdehyde from lipid peroxides in rat brain homogenate, and reduced lipid peroxidation by the free radical generating system of xanthine-xanthine oxidase. Indeed, the scavenging action of indapamide significantly attenuated the inhibitory activity of 15-hydroperoxy-arachidonate to prostacyclin synthase activity. These results indicate that indapamide diuretic increases prostacyclin generation in the vascular smooth muscle cells possibly through antioxidant effects and that the enhanced prostacyclin generation is partly responsible for its direct vasodilator action.
Hypertension 1990 Feb
PMID:Radical scavengers of indapamide in prostacyclin synthesis in rat smooth muscle cell. 210 10

Thiazide diuretics are particularly efficacious in the treatment of hypertension in blacks. A number of observations suggest that many hypertensive blacks have features consistent with a status of "corrected" volume expansion. Our studies, as well as those of other investigators, show that the Na,K pump is inhibited in leucocytes and erythrocytes of blacks with essential hypertension. This observation is also consistent with the concept of volume expansion in hypertensive blacks, since the Na,K pump is inhibited in many forms of experimental volume expansion, including the administration of salt in normal humans. We postulate that the efficacy of thiazide diuretics may be related to their ability to stimulate the Na,K pump. We present data obtained in 13 black hypertensive men in whom Na efflux, and Na,K-ATPase in the erythrocyte rose significantly after 7 days of treatment with hydrochlorothiazide, 50 mg/day. Diuretic therapy may indirectly result in reduced intracellular calcium in the vascular smooth muscle.
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PMID:Diuretics and cation transport in hypertensive blacks. 217 10

Thiazide diuretic receptor density was assessed in kidneys from spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats by measuring hydroflumethiazide-displaceable 3H-metolazone binding to renal membranes in vitro. Renal thiazide receptor density was not significantly different in 4 week old SHR and WKY rats, but was significantly increased by 20%-40% in 14-49 week old SHRs compared to WKY rats. Affinity of receptors for 3H-metolazone did not differ between SHRs and WKY rats at any age. In WKY rats with 2 kidney-1 clip (2K-1C) hypertension, thiazide receptor density was not significantly different in either clipped or unclipped kidneys from sham-operated controls. Thus, increased renal thiazide receptor density occurs in SHRs along with the development of hypertension and does not appear to be secondary to increased renal perfusion pressure. This increase may reflect altered hormonal or ionic input to the distal tubule and may contribute to elevated sodium reabsorption in this segment in the SHR.
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PMID:Thiazide diuretic receptors in spontaneously hypertensive rats and 2-kidney 1-clip hypertensive rats. 234 95


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