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

Endothelium-dependent vasorelaxation is defective in hypertensive rats, especially in conduit arteries. In the stroke-prone spontaneously hypertensive rat, impaired endothelium-dependent vasorelaxation appears to contribute to the pathogenesis of stroke independent of blood pressure. Because treatment with lacidipine, a long-acting calcium channel blocker, protects against stroke and cardiovascular remodeling in this model, we investigated the effect of this treatment on endothelium-dependent vasorelaxation in the aorta. Stroke-prone rats were exposed to a salt-rich diet (1% NaCl in drinking water) with or without lacidipine (1 mg. kg(-1). d(-1)) for 6 weeks. A high-sodium diet (1) increased systolic blood pressure, aortic weight, and wall thickness and plasma renin activity (P<0.05); (2) markedly reduced nitric oxide (NO)-mediated, endothelium-dependent relaxation of aortic rings to acetylcholine and the sensitivity to the relaxing effect of S-nitroso-N-acetylpenicillamine, an NO donor (P<0.001); and (3) induced an elevation of preproendothelin-1 mRNA levels in aortic tissue (P<0.01) without affecting endothelial NO synthase mRNA levels. Lacidipine treatment prevented the salt-dependent functional and structural alterations of the aorta, including the overexpression of the preproendothelin-1 gene, and increased endothelial NO synthase mRNA levels in aortic tissue (P<0.01). In conclusion, lacidipine protects stroke-prone hypertensive rats against the impairment of endothelium-dependent vasorelaxation evoked by a salt-rich diet, and this effect may contribute to its beneficial effect against end-organ damage and stroke.
Hypertension 2001 Apr
PMID:Lacidipine prevents endothelial dysfunction in salt-loaded stroke-prone hypertensive rats. 1130 13

Cyclosporine (CsA) treatment in solid organ transplantation has represented one of the greatest advances in the past 20 years, reducing acute rejection and increasing long-term survival. However, CsA has an important side effect, producing renal vasoconstriction and systemic hypertension. The main histological findings in the kidney are vascular lesions in the endothelium and smooth muscle cells. On proximal tubule cells, severe atrophy, vacuolization and thickening of the basal membrane can be found. The main mechanisms of vasoconstriction are secondary to endothelium disorders, increasing vasoconstrictor substances like endothelin, thromboxane, free radicals, etc., and reducing vasodilator substances like nitric oxide and prostaglandins. CsA acute nephrotoxicity produces haemodynamic changes with minor histological lesions, which will disappear when the medication is discontinued. Long-term CsA nephrotoxicity has been widely discussed in the literature. For some authors, a limited number of patients can develop end-state renal failure but others did not suffer these complications. Nevertheless, it seems clear that high doses of CsA can produce renal lesion and renal insufficiency, being difficult to evaluate in renal transplant patients because of the frequent association with chronic rejection lesions. Several types of drugs have been used to treat CsA nephrotoxicity in renal transplant patients but calcium antagonists and angiotensin converting enzyme-inhibitors are the most frequently used, especially the former due to their effect on the afferent arteriole vasodilatation, their natriuretic properties and their reducing intracellular calcium. The greatest experience has been with nifedipine, but other drugs like verapamil, diltiazem, amlodipine, felodipine, isradipine, etc., have also been used. Lacidipine, a 1,4-dihydropiridine, has demonstrated a beneficial effect during the short term after renal transplantation, and a multicentre, multinational, double-bind, placebo-controlled clinical trial for the long term currently ongoing.
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PMID:Calcium antagonists and renal protection from cyclosporine nephrotoxicity: long-term trial in renal transplantation patients. 1134 60

The photostability of Lacidipine, a dihydropyridine drug used in the treatment of mild and moderate hypertension, was studied in solutions exposed to UV-A radiations. The effects of the solvent (ethanol, acetone, dichloromethane), drug concentration and radiation wavelength on the drug photostability were evaluated. Lacidipine and its photoproducts were separated by a selective liquid chromatographic (HPLC) method, under normal phase conditions (CN-column), using n-hexane:ethanol 97:3 (v/v) as mobile phase, at a flow rate of 2.0 ml/min. The main photodegradation products were isolated and characterised and a photodegradation pathway was proposed for Lacidipine in solution. The cis-isomer and a photocyclic isomer proved to be the main photodegradation products.
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PMID:Photodegradation studies on lacidipine in solution: basic experiments with a cis-trans reversible photoequilibrium under UV-A radiation exposure. 1181 21

Dihydropyridines can inhibit gene expression in-vitro and may have a protective vascular effect independent of blood pressure reduction. We tested the hypothesis that lacidipine prevents induction of inducible NO synthase (iNOS), influences leukocyte adhesion and infiltration, inhibits nuclear factor (NF)-kappaB transcription factor activity, and ameliorates end-organ damage in a transgenic rat model of angiotensin (Ang) II--dependent organ sclerosis. We treated rats transgenic for human renin and angiotensinogen (dTGR) from week 4 to 7 with lacidipine (0.3 or 3 mg/kg by gavage). Blood pressure was measured by tail cuff. Organ damage was assessed by histology and immunohistochemistry. Adhesion molecules and cytokines were analyzed by immunohistochemistry. Transcription factors were analyzed by mobility shift assays. Untreated dTGR developed moderate hypertension, cardiac hypertrophy, and severe renal damage with albuminuria. Lacidipine decreased blood pressure slightly at the low dose and substantially at the higher dose. However, both treatments reduced albuminuria and plasma creatinine to the same degree (P<0.05). Intercellular adhesion molecule-1 (ICAM-1) was markedly reduced by lacidipine as well as renal neutrophil and monocyte infiltration. Lacidipine reduced mitogen-activated protein (MAP) kinase phosphorylation and iNOS expression in both cortex and medulla. NF-kappaB and AP-1 were activated in dTGR but reduced by lacidipine. Lacidipine ameliorates Ang II-induced end-organ damage independent of blood pressure lowering, perhaps by inhibiting the MAP kinase pathway and NF-kappaB activation.
Hypertension 2002 Feb
PMID:Lacidipine inhibits adhesion molecule and oxidase expression independent of blood pressure reduction in angiotensin-induced vascular injury. 1188 31

Lacidipine is a clinically active, antihypertensive calcium antagonist of the 1,4 dihydropyridine (DHP) class. It is also capable of vascular protection when administered (prophylactically and therapeutically) at nonsustained antihypertensive doses to salt-sensitive Dahl-S rats: useful animal models for studying the vasoprotective effect of calcium antagonists. In our previous work using voltammetry with selective biosensors, we observed that lacidipine implements endothelial nitrogen monoxide (NO) in normal rats. These experiments, performed in aortic rings obtained from Dahl-S rats analyzed with voltammetry and specific biosensors, further demonstrate that lacidipine, given at doses that do not control the development of hypertension (1 mg/kg), enhance endothelial NO activity. Taken together with the observation that 1 mg/kg lacidipine, and not its vehicle, is able to prevent vascular damage and concomitant increases in mortality (accelerated by a salt diet), this voltametric data suggest that NO acts as a component of positive influence of this DHP on vascular structure and function.
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PMID:Evidence that lacidipine at nonsustained antihypertensive doses activates nitrogen monoxide system in the endothelium of salt-loaded Dahl-S rats. 1190 20

Lacidipine, a third generation dihydropyridine calcium antagonist, has demonstrated pronounced anti-atherosclerotic activity in preclinical studies. The drug can act at several stages within the atherosclerotic process, utilising its antihypertensive and antioxidant properties to protect hypertensive animals against mortality and vascular damage, to reduce cholesterol levels from the vessel wall of hypercholesterolaemic animals, and to reduce the progression of existing atherosclerotic lesions. The clinical benefit of lacidipine in atherosclerosis has recently been confirmed in humans in a large, multicentre, comparative, 4-year clinical trial involving patients with mild to moderate hypertension. The European Lacidipine Study on Atherosclerosis (ELSA) showed that lacidipine was able to slow the progression of atherosclerosis, measured as carotid intimato-media thickness, by 40% compared with atenolol (p = 0.0073). Although further comparative trials are needed, based on the results of ELSA, lacidipine is likely to become a promising therapeutic agent for atherosclerosis.
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PMID:Endothelial dysfunction, hypertension and atherosclerosis. A review of the effects of lacidipine. 1245 52

Similarities and dissimilarities of 3 third generation calcium antagonist (amlodipine, lacidipine and lercanidipine) are presented. Lacidipine is characterized by prolonged antihypertensive action despite its plasma half life is just about 14 hours. Duration of lacidipine effect can be explained by accumulation in lipid bilayer of cellular membranes where it interacts with calcium channels. Pharmacodynamics of lacidipine is discussed in detail as well as experience of its use in hypertension including data of ELSA study which has demonstrated ability of lacidipine to inhibit progression of carotid artery atherosclerosis.
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PMID:[Third generation of calcium antagonists: focus on lacidipine]. 1249 25

Inflamed tissues are often characterised by the production of *NO and O(2)(-) radicals, which are known to react at an extremely fast rate to produce peroxynitrite (ONOO(-)). This highly oxidising entity reacts with protein-bound tyrosine to give 3-nitrotyrosine, which is considered a biochemical marker of peroxynitrite-induced damage. Lacidipine is a calcium antagonist indicated for the treatment of mild to moderate hypertension. In the present work, electrospray mass spectrometry with and without liquid chromatography was used to evaluate the capability of lacidipine and two other related molecules as ONOO(-) scavengers. This capability is compared with that associated with a number of commercial polyphenols described in the literature as efficient scavengers of this cytotoxic agent. The use of mass spectrometry provided rapid quantitative assessment of both the nitration and its reduction, and showed that lacidipine possesses a reasonable capability for reducing in vitro nitration of superoxide dismutase.
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PMID:Lacidipine, a potential peroxynitrite scavenger: investigation of activity by liquid chromatography and mass spectrometry. 1256 35

Oxidized low-density lipoprotein (OxLDL) and autoantibodies to OxLDL (aOxLDL) are implicated in the development of atherosclerosis. The objective of this study was to determine the importance of these factors in hypertension, a major risk factor for atherosclerosis. Samples were obtained from 111 men with established hypertension (diastolic pressure >95 mmHg) from the Swedish component of an ongoing hypertension study (European Lacidipine study on Atherosclerosis, ELSA) and from 75 normotensive control men, who were from a Swedish population-screening programme (diastolic pressure <80 mmHg). The presence of carotid atherosclerosis and the intima-media thicknesses were determined by ultrasonography. A monoclonal antibody to OxLDL, EO6, was used to determine oxidation epitopes in LDL. aOxLDL of IgG and IgM subclass were tested by ELISA against OxLDL. Hypertensive men had increased OxLDL levels compared with normotensives ( P =0.002), whereas autoantibodies tested were largely similar between groups. There was no association between the antibodies tested, or OxLDL and carotid atherosclerosis. Age was not associated with OxLDL or aOxLDL measurements. Taken together, our findings indicate that OxLDL is elevated in hypertensive men, which may predispose to atherosclerosis in hypertension. In contrast, aOxLDL levels were unchanged and the role of aOxLDL may depend on disease stage and/or type.
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PMID:Circulating oxidized low-density lipoprotein is increased in hypertension. 1283 27

Although heat shock proteins (Hsp's) are present in the sera of healthy individuals and at elevated levels in subjects with early cardiovascular disease, their physiologic role in and value for predicting the development and/or progression of atherosclerosis have not been evaluated. Serum was obtained from 218 subjects with established hypertension (diastolic pressure >95 mm Hg) before their enrollment in the European Lacidipine Study on Atherosclerosis. Hsp60 and Hsp70, and anti-human Hsp60, anti-human Hsp70, and anti-mycobacterial Hsp65 antibody levels were measured by enzyme immunoassay. As an indicator of the presence/progression of atherosclerosis, the means of the maximum intima-media (I-M) thicknesses in the far walls of common carotid arteries and bifurcations (CBMmax) were determined by ultrasonography at the time of enrollment and 4 years afterward. Increases in I-M thicknesses at follow-up were less prevalent in subjects having high serum Hsp70 levels (75th percentile) at the time of enrollment (odds ratio, 0.42; 95% confidence interval [CI], 0.22 to 0.8, P=0.008). Although a similar trend was observed for serum Hsp60 levels, this was not statistically significant (odds ratio, 0.6; 95% CI, 0.32 to 1.11, P=0.10). There was no relation between anti-Hsp antibody levels and changes in I-M thicknesses. The relation between Hsp70 levels and changes in I-M thickness was independent of age, atenolol or lacidipine treatment, smoking habits, and blood lipid levels. These findings indicate that circulating Hsp70 levels predict the development of atherosclerosis in subjects with established hypertension, and an intriguing possibility is that Hsp70 protects against or modifies the progression of atherosclerosis in this subject group.
Hypertension 2003 Sep
PMID:Serum heat shock protein 70 levels predict the development of atherosclerosis in subjects with established hypertension. 1475 85


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