Effect of Pravastatin on Proteinuria in Patients With Well-Controlled Hypertension

Lee, Tsung-Ming; Su, Sheng-Fang; Tsai, Chang‐Her

doi:10.1161/01.hyp.0000022805.11288.7f

Cited by 108 publications

(61 citation statements)

References 41 publications

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“…[23][24][25] In contrast, studies including normotensive individuals or well-controlled hypertensive patients were unable to demonstrate a statin-induced blood pressure-lowering effect. 26,27 In agreement with these latter studies, no blood pressure-lowering effect of fluvastatin was observed in our normotensive FH subjects. The reason for the absence of a blood pressure-lowering effect despite the decrease in Ang II sensitivity is unknown.…”

Section: Van Der Linde Et Al Ldl Cholesterol and Ang II Sensitivitysupporting

confidence: 92%

Effect of Low-Density Lipoprotein Cholesterol on Angiotensin II Sensitivity

et al. 2006

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Abstract-Increased angiotensin II (Ang II) sensitivity predisposes to hypertension and plaque instability. Raised low-density lipoprotein cholesterol (LDL-c) may increase Ang II sensitivity, but evidence in humans for this effect of LDL-c is limited. In 28, healthy, nonsmoking subjects, aged 30Ϯ8 years, with familial hypercholesterolemia, we determined the difference in infusion rate of Ang II and norepinephrine required to increase systolic blood pressure by 20 mm Hg (Pd-20) after 4 weeks of placebo and fluvastatin 80 mg daily in a randomized, double-blind, placebocontrolled, crossover study. Before infusions were started, fasting blood samples were taken to measure lipids. After 4 weeks of placebo, the mean LDL-c concentration was 6.3Ϯ1.4 mmol/L. [2][3][4][5] Moreover, an AT 1 -receptor antagonist inhibited LDL oxidation and streak formation in hypercholesterolemic monkeys. 6 In vitro and animal data support the idea that raised LDL-c associates with increased AT 1 -receptor gene expression in vascular smooth muscle cells. 7,8 Evidence for a direct effect of raised LDL-c on the sensitivity to Ang II in humans is limited. In previous studies we analyzed older subjects with additional cardiovascular risk factors, like hypertension and the metabolic syndrome, that could explain the increased sensitivity to Ang II as well. 9 -11 Proof of a direct effect of LDL-c on Ang II sensitivity could have preventive implications. We hypothesized that raised LDL-c increases sensitivity to Ang II, and, conversely, lowering LDL-c levels should decrease this sensitivity.In the present randomized, double blind, placebo-controlled crossover study, the effect of fluvastatin on Ang II sensitivity was assessed in healthy, young subjects with familial hypercholesterolemia (FH). FH is a monogenetic disorder characterized by markedly raised LDL-c levels. Methods SubjectsWe used predefined criteria to recruit 30 healthy, young, nonsmoking FH subjects without signs of cardiovascular disease. The diagnosis FH was based on LDL-c above age-and sex-specific 95th percentiles during a cholesterol-lowering diet with triglycerides and HDL-cholesterol (HDL-c) within the normal limits and a molecular diagnosis or the presence of tendon xanthomas or hypercholesterolemia in Ն1 first-degree relative. 12 Exclusion criteria were secondary forms of hypercholesterolemia, hypertension, obesity, a history or signs of cardiovascular disease, smoking during the year before the trial, a history of alcohol or drug abuse, or noncompliance to treatment.To obtain normal reference values, we previously studied 10 untreated, healthy, normocholesterolemic volunteers (6 males) matched as group for age (28Ϯ11 years), blood pressure (123Ϯ10/75Ϯ10 mm Hg), and body mass (23.4Ϯ2.0 kg/m 2 ), who underwent an identical protocol as the subjects of the present study. 13 Their fasting values of LDL-c, high-density lipoprotein (HDL) cholesterol (HDL-c), triglycerides and glucose were, respectively, 2.2Ϯ0.7 mmol/L, 1.4Ϯ0.6 mmol/L, 0.9Ϯ 0.8 mmol/L, and 3.8Ϯ0.4 mmol/L. The study...

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Section: Van Der Linde Et Al Ldl Cholesterol and Ang II Sensitivitysupporting

confidence: 92%

Effect of Low-Density Lipoprotein Cholesterol on Angiotensin II Sensitivity

et al. 2006

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“…Immunoglobulins have been found in the urine of human patients with glomerular disease in a variety of disorders (4,3,25,29). Moreover, several infectious diseases are diagnosed by the finding of specific antibodies in urine, such as Helicobacter pylori infection (18), filariasis (17), or schistosomiasis (35).…”

Section: Discussionmentioning

confidence: 99%

Detection of Anti-LeishmaniaImmunoglobulin G Antibodies in Urine Specimens of Dogs with Leishmaniasis

Solano‐Gallego

Rodríguez

Iniesta

et al. 2003

Clin Vaccine Immunol

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For years, anti-Leishmania immunoglobulin G (IgG) antibodies have been detected in the sera of dogs living in areas of leishmaniasis endemicity. They have also been found in the aqueous humor and cerebrospinal fluid. In contrast, a review of the literature failed to identify the detection of anti-Leishmania antibodies in urine samples from dogs with leishmaniasis. Ninety-five dog urine samples were examined for the presence of anti-Leishmania antibodies by using a protein A enzyme-linked immunosorbent assay (ELISA). Twenty additional urine samples were collected from healthy dogs as controls. An IgG2 ELISA was performed on 26 urine samples found positive by the protein A ELISA. Twenty-three urine samples found positive to anti-Leishmania antibodies were tested for the local production of anti-Leishmania antibodies in the urinary tract by means of the urine antibody coefficient. Ten urine samples (and the corresponding serum samples) were compared by Western blot (WB) analysis. Thirty-five out of the 95 urine samples were found positive, 57 were found negative, and 3 were found inconclusive for antibody detection by the protein A ELISA. A high correlation between protein A and IgG2 levels was found in positive urine samples. Anti-Leishmania antibodies were present in the urine of dogs that had leishmaniasis, urinary protein/creatinine (U P/C) ratios of greater than one, and normal urinary sediment. A statistically significant correlation was observed between the U P/C ratios and the levels of anti-Leishmania antibodies in positive urine samples. In general, WB analysis and the urine antibody coefficient suggested that the presence of anti-Leishmania antibodies in urine was the consequence of an impairment of filtration of the glomerular barrier. However, in some dogs, WB analysis could be interpreted as suggesting that the presence of anti-Leishmania antibodies was caused, to a lesser extent, by local antibody production in the urinary tract. Antibody detection in urine could be a noninvasive method for leishmaniasis diagnosis and prognosis in dogs with glomerulonephropathies.Canine leishmaniasis, caused by the protozoan parasite Leishmania infantum, is a severe systemic disease highly prevalent in the Mediterranean basin. Clinical manifestations of the disease include nonpruritic skin lesions, such as exfoliative dermatitis and ulcerations; local or generalized lymphadenopathy; loss of weight; poor appetite; ocular lesions; epistaxis; lameness; renal failure; and diarrhea (8,12,21,36). Dogs with leishmaniasis have high anti-Leishmania immunoglobulin G (IgG) antibody levels in sera (23), and clinicopathological findings include anemia, hypoalbuminemia, hyperglobulinemia, hypercreatinemia, and proteinuria (22).In the vast majority of cases, the fatal course of canine leishmaniasis is due to renal involvement (5, 32). The major renal lesion in canine (32) and human (7, 11) leishmaniasis is glomerulonephritis. However, interstitial nephritis, tubular nephropathy, and glomerular amyloidosis in conjunction with glomer...

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“…Intra-and interassay coefficients of variation were 4.5% and 6.6%, respectively. Total serum cholesterol and triglyceride levels were measured by standard enzymatic techniques (18).…”

Section: Methodsmentioning

confidence: 99%

“…Statin therapy has many effects independent of changes in plasma cholesterol concentrations (18). Lipophilic statins have been shown to attenuate in vitro cellular hypertrophy (21,27).…”

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confidence: 99%

Effect of simvastatin on left ventricular mass in hypercholesterolemic rabbits

Lee¹,

Lin²,

Chou³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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Lee, Tsung-Ming, Mei-Shu Lin, Tsai-Fwu Chou, and NenChung Chang. Effect of simvastatin on left ventricular mass in hypercholesterolemic rabbits. Am J Physiol Heart Circ Physiol 288: H1352-H1358, 2005. First published October 14, 2004 doi:10.1152/ ajpheart.00527.2003.-Epidemiological studies showed that hypercholesterolemia is associated with higher left ventricular mass. Endothelin signaling is activated in hyperlipidemic animals and may contribute to progressive ventricular hypertrophy. Simvastatin has been shown to inhibit endothelin-1. However, the behavior of simvastatin on ventricular hypertrophy in hyperlipidemic animals is not well understood. In this study, we evaluated the hemodynamic, biochemical, and morphological responses to simvastatin in cholesterol-fed (1%) rabbits. The left ventricular weight increased 8 wk after cholesterol feeding compared with that in normocholesterolemic rabbits. Simvastatin at a clinical therapeutic dose (1.2 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) significantly decreased left ventricular weight by 14% and left ventricular myocyte sizes by 14% as isolated by enzymatic dissociation. Hypercholesterolemia upregulated ventricular preproendothelin-1 mRNA as assessed by real-time quantitative RT-PCR and elevated production of cardiac endothelin-1 concentration. The increased endothelin-1 responses can be inhibited after simvastatin administration. Left ventricular mass indexed by body weight positively correlated with tissue endothelin-1 levels (P ϭ 0.0003). In Langendorff-perfused rabbit hearts, hyperlipidemia led to significant QT prolongation compared with normocholesterolemia, which can be reversed by administering simvastatin. In contrast, simvastatin-induced beneficial effects were reversed by the addition of mevalonate. The addition of bosentan, a nonspecific endothelin receptor blocker, improved the response in hypercholesterolemic rabbits and did not have additional beneficial effects in simvastatin-treated rabbits. The results of the present study suggest that the antihypertropic and electrocardiographic effects of simvastatin at a clinical therapeutic dose are mediated through inhibition of tissue endothelin-1 expression, which is linked to mevalonate metabolism, and result in an amelioration of cardiomyocyte hypertrophy development by an atherogenic diet.electrocardiogram; endothelin-1; hyperlipidemia; rabbit WE (16) and others (33) have demonstrated that dyslipidemia is an independent determinant of increased left ventricular (LV) mass. Myocardial hypertrophy is an adaptation response of the heart to increased work load. However, increased LV mass is a risk factor of cardiac morbidity and mortality in the general population (4). Previous data have revealed that LV mass regression reduced cardiovascular complications (4). Thus reversal of LV mass is widely accepted as a desirable treatment goal. There is considerable evidence that electrophysiological changes are associated with the hypertrophied myocardium, such as an increased QT interval (29). QT interval prolongation, even within ...

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Effect of Pravastatin on Proteinuria in Patients With Well-Controlled Hypertension

Cited by 108 publications

References 41 publications

Effect of Low-Density Lipoprotein Cholesterol on Angiotensin II Sensitivity

Effect of Low-Density Lipoprotein Cholesterol on Angiotensin II Sensitivity

Detection of Anti-LeishmaniaImmunoglobulin G Antibodies in Urine Specimens of Dogs with Leishmaniasis

Effect of simvastatin on left ventricular mass in hypercholesterolemic rabbits

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