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

In order to compare the protective effects of angiotensin converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB) on the renal function in experimental nephritis, nephrotoxic serum nephritis was induced in male spontaneously hypertensive rats (SHR). The above drugs were then chronically administered to different groups, as follows: the ACEI-treated group (n = 7) received captopril (150 mg/kg/day), and the CCB-treated group (n = 6) was given both nifedipine (40 mg/kg/day) and nisoldipine (20 mg/kg/day). The control group (n = 8) received a placebo. Although the control group developed marked hypertension and proteinuria, the rats treated with either ACEI or CCB demonstrated a significant and equivalent decrease in mean arterial pressure and urinary protein excretion. At 15 weeks after the injection of nephrotoxic serum, all rats were anesthetized with Inactin, and the glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured. In the control group, GFR and RPF were markedly attenuated. However, both were preserved at much higher levels in the ACEI-treated group, and GFR was also maintained to a similar degree in the CCB-treated group. Histological studies were carried out after the clearance studies. As a result, it was found that the ACEI treatment significantly limited the development of glomerulosclerosis, whereas CCB modestly ameliorated the glomerular structural lesions. Moreover, ACEI significantly reduced the serum cholesterol, while CCB did not exert such an effect. These results suggest that both ACEI and CCB have a therapeutic effect in experimental glomerulonephritis models which are accompanied by hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of converting enzyme inhibitor and calcium channel blocker in SHR with nephrotoxic serum nephritis. 163 85

The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Aug
PMID:Adverse effect of the calcium channel blocker nitrendipine on nephrosclerosis in rats with renovascular hypertension. 163 66

Endothelins (ETs) are a recently discovered family of small proteins that have potent long-lasting vasoconstrictive activities. Increased circulating concentrations of ETs have been found in hypertensive and renal disorders, including pregnancy-induced hypertension (PIH). PIH has been postulated to be the end result of endothelial cell damage and aberrant calcium metabolism. We evaluated the effects of calcium ionophores, calcium channel blockers, and two forms of cellular damage on ET production by human umbilical vein endothelial cells (HUVEC). Cells were grown to confluence and then incubated for 16 h with these treatments: physical trauma ("scratching"), oxidant damage (hydrogen peroxide, 1-20 mM), ionomycin (0.25-2.0 microM), A-23187 (10(-9)-10(-5) M), verapamil (0.22-22.0 microM), and nifedipine (2-200 micrograms/mL). ET production was determined using a commercial RIA that detects ET-1 and ET-2. Physical trauma enhanced ET production, whereas oxidant damage had the opposite effect. Both ionomycin and A-23187 caused concentration-dependent inhibition of ET production. Neither verapamil nor nifedipine consistently altered ET production. We conclude that specific forms of cellular damage can stimulate HUVEC ET production, although oxidant damage may be slightly inhibitory. Thus, enhanced ET levels in PIH may represent endothelial cell activation, rather than damage. HUVEC ET production is regulated in an inverse manner by intracellular calcium concentrations, suggesting a negative feedback from mediators of ET action on cells.
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PMID:The regulation of endothelin production in human umbilical vein endothelial cells: unique inhibitory action of calcium ionophores. 163 63

African Americans have a higher prevalence of hypertension than white Americans. Morbid consequences of hypertensive disease are greater in blacks than whites. For members of high-risk groups such as blacks, ambulatory blood pressure monitoring may be useful in supplementing casual clinic measurements to prevent misdiagnosis, better characterize the temporal topography of blood pressure responses, and improve prediction of left ventricular hypertrophy, hypertensive complications, morbidity, and mortality. In conjunction with other data, laboratory experiments showing that African Americans as a group show greater peripheral resistance and slowed natriuretic responses to behavioral stressors than whites, appear to provide insights as to why blacks generally respond better to diuretics and calcium channel blockers than to beta-adrenergic antagonists or angiotensin-converting enzyme inhibitors. It is suggested that ambulatory blood pressure monitoring and behavioral tasks in the laboratory may help predict individual responsiveness to antihypertensive agents.
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PMID:Ethnicity and ambulatory blood pressure measurement: relationship to clinic and laboratory measurements. 163 97

Moderate pyridoxine deficiency in rats has been shown to induce hypertension, which can be corrected by pyridoxine supplementation. In this study, calcium handling by isolated caudal arteries from pyridoxine-deficient and age-matched control rats was evaluated. We found 45Ca influx into the intracellular compartment to be significantly elevated in deficient rats. This increased influx could be attenuated with nifedipine, a calcium channel blocker, in a dose-dependent manner, suggesting alterations in the calcium channels that would make them leaky. The pyridoxine-deficient arterial segments maintained a higher resting tone; removal of extracellular calcium by EGTA or entry blockade by nifedipine decreased the tone significantly in the deficient arteries, compared with little or no effect in controls.
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PMID:Increased calcium influx in caudal artery of rats made hypertensive with pyridoxine deficiency. 164 79

The majority of second-generation calcium antagonists are dihydropyridines, some of which show vascular selectivity. Several new dihydropyridines have been developed with comparable pharmacodynamic properties to existing calcium antagonists in this class and greatly improved kinetic half-lives. Of these agents, amlodipine has by far the longest half-life (30-40 h) allowing the benefit of once-daily administration; it has the additional property of a slow association and dissociation with the calcium channel binding site. In the treatment of hypertension and myocardial ischaemia the prolonged duration of action distinguishes amlodipine from other second-generation agents.
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PMID:Profiles of calcium antagonists in cardiovascular disease with special reference to second-generation agents and amlodipine. 166 30

Several antihypertensive agents have been found to influence serum lipid profiles. Thiazide diuretics increase total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and slightly reduce high-density lipoprotein (HDL) cholesterol. Most beta-blockers substantially increase triglycerides and lower HDL cholesterol. Angiotensin-converting enzyme inhibitors, calcium channel antagonists, alpha- and beta-blockers, and beta-blockers with intrinsic sympathomimetic activity are lipid neutral. alpha 1-Antagonists (e.g., terazosin and prazosin) lower total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and improve total cholesterol/HDL ratios. Observational epidemiologic studies indicate that the lipid effects of antihypertensive agents are large enough to account for substantial differences in the predicted incidence of coronary heart disease. Combination therapy with the alpha 1-antagonist terazosin plus either thiazides or beta-blockers also ameliorates the adverse lipid effects of these agents used alone. A reasonable approach to managing the lipid problems often associated with hypertension is to advise a cholesterol-lowering, low-sodium diet and weight reduction and to select drugs that alone or in combination do not adversely affect lipid profiles.
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PMID:Antihypertensive therapy: taking lipids into consideration. 167 22

The main aim of the treatment of hypertension is to reduce the incidence and severity of its complications. Despite some bias affecting the major clinical trials of diuretics and/or beta blockers, the results of the meta-analysis taking them into account demonstrate the effectiveness of the prevention of cerebrovascular complications and the less effective prevention of coronary complications. Progress can be hoped for as a result of new therapeutic categories (converting enzyme inhibitors, calcium channel inhibitors ...) and to a greater extent from new treatment strategies, involving better identification of "genuinely high risk" subjects.
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PMID:[Do antihypertensive agents change the incidence of cardiovascular complications of hypertension?]. 168 78

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

Primary cultures of neonatal rat cardiocytes were exposed for 24 hours to culture media containing 0-2.0 mM extracellular calcium. Both atrial natriuretic factor (ANF) messenger RNA (mRNA) and ANF secretion were increased approximately threefold in the presence of 2.0 mM CaCl2 (vs. Ca2(+)-free medium). When cardiocytes were treated with the calcium channel blockers diltiazem, nifedipine, or verapamil, both ANF synthesis and secretion fell to 25-40% of control values. The choice of transcription start site on the ANF gene was not altered by the calcium channel blockers. When exogenous calcium was added to cardiocytes treated with verapamil, secretion of ANF was partially restored to control levels. High-performance liquid chromatographic analysis of medium from cardiocytes exposed to varying extracellular calcium concentrations or treated with calcium channel blockers for 24 hours revealed that the majority of secreted immunoreactivity (60-70%) migrated with pro-ANF (17 kDa) and that none of the various experimental manipulations significantly changed the ratio of pro-ANF to ANF in the media. These results were confirmed by immunoprecipitation analysis of the culture medium from the individual treatment groups. Treatment of cardiocytes for 24 hours with either the calcium ionophore A23187 or the phorbol ester 12-O-tetradecanoylphorbol 13-acetate increased ANF secretion. The combined use of these agents resulted in stimulation of both ANF secretion and ANF mRNA accumulation.
Hypertension 1990 Jan
PMID:Extracellular calcium regulates expression of the gene for atrial natriuretic factor. 168 46


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