Effect of Antihypertensive Drugs on Uric Acid Metabolism in Patients with Hypertension: Cross-Sectional Cohort Study.

Background: Hypertension is a common complication in patients with gout and/or hyperuricemia. Besides, hyperuricemia is a risk factor of gout as well as ischemic heart disease in hypertensive patients. Moreover, the risk of gout is modified by antihypertensive drugs. However, it remains unclear how antihypertensive agents affect uric acid metabolism. Purpose: In the present study, we investigated the uric acid metabolism in treated hypertensive patients to find out whether any of them would influence serum levels of uric acid. Patients and methods: 751 hypertensive patients (313 men and 438 women) under antihypertensive treatment were selected. Blood pressure (BP), serum uric acid (SUA) and serum creatinine (Scr) were measured and evaluated statistically. Results: In patients treated with diuretics, beta-blockers and/or alpha-1 blockers SUA levels were significantly higher than in patients who were not taking these drugs. Besides, the estimated glomerular filtration rate (eGFR) in patients treated with diuretics, beta-blockers and/or alpha-1 blockers was negatively correlated with SUA level. There were gender differences in the effects of beta-blockers and alpha-1 blockers. Multiple regression analysis indicated that both diuretics and beta-blockers significantly contributed to hyperuricemia in patients with medication for hypertension. Conclusion: Diuretics, beta-blockers and alpha-1 blockers reduced glomerular filtration rate and raised SUA levels. Calcium channel blockers, ACE inhibitors and angiotensin receptor blockers, including losartan, did not increase SUA levels.

Effect of glucose concentration on foam cell formation in THP-1 cells.

We investigated whether a high glucose condition could affect cholesterol ester (CE) synthesis and accumulation of cholesterol in arterial wall cells by using the human monocytic cell line THP-1. After 24-hour PMA treatment, cells were grown in control (200 mg/dl of glucose) or high glucose concentration (400, 600, 800, or 1,600 mg/dl) medium for 6 days. CE synthesis was then investigated in cells incubated with 50 microg/ml of native, glycated, acetylated, or oxidized LDL. Cells grown in 400 mg/dl of glucose showed a significant increase of CE synthesis regardless of whether they were incubated with native, glycated or oxidized LDL, compared with cells grown in 200 mg/dl of glucose. In parallel with the studies of CE synthesis, the intracellular accumulation of CE also increased in cells grown in 400 mg/dl of glucose when incubated with oxidized LDL (50 microg/ml), compared with that in cells grown in 200 mg/dl of glucose. The amount of oxidized LDL associated with cells grown in 400 mg/dl of glucose was markedly higher than that in cells grown in 200 mg/dl of glucose. This suggests that there is an optimal glucose concentration (400 mg/dl) which increases the number of some scavenger receptors (receptors for oxidized LDL) expressed on cells, and might increase and stimulate CE synthesis, resulting in intracellular accumulation of CE in macrophage. A high blood glucose concentration could change the metabolism of arterial wall cells and play an important role in the pathogenesis of vascular complications of diabetes mellitus.

[Syndrome X].

Insulin resistance is an early and major feature in the development of non-insulin-dependent diabetes mellitus(NIDDM). It is also associated with hyperlipidemia, hypertension, obesity and cardiovascular disease. It is the clustor of the risk factors for atherosclerosis and recognized as 'insulin-resistance syndrome' (Syndrome X). Central (abdominal) obesity is much more strongly associated with insulin resistance than overall obesity. The increase of both the influx of free fatty acid to liver and the production of TNF-alpha in adipose tissue may play an important role in mechanism of insulin resistance associated with central obesity. Calorie restriction and weight loss improve insulin sensitivity in overweight humans. Exercise training also improves insulin sensitivity via increased oxidative enzymes, glucose transporters (GLUT4) and capillarity in muscle as well as by reducing abdominal fat. The new 'glitazones' (thiazolidinediones) is used clinically to improve insulin sensitivity.

Antigen-induced elevation of immunoreactive endothelin-1 (ET-1) levels in ovalbumin-sensitized guinea pig airway tissue.

Changes in the immunoreactive ET-1 levels during the anaphylactic reaction of airway tissue from ovalbumin-sensitized guinea pigs were investigated. ET-1-immunoreactivity (ET-IR) was detected in the epithelial and smooth muscle layers of tracheal sections from normal guinea pigs and it was enhanced slightly by phosphoramidon (1 microM) treatment. The ET-IR level of the epithelial layer of ovalbumin-treated tissue from actively sensitized animals was slightly higher than that from normal animals, but it was enhanced markedly by phosphoramidon (1 microM) treatment. Furthermore, the mean ET-IR level of homogenates of antigen-treated tracheal tissues from sensitized guinea pigs (22.8 +/- 1.55 fmol mg-1 protein, n = 5) was significantly higher than the corresponding normal level (12.3 +/- 1.21 fmol mg-1 protein, n = 5). These results suggest that increased epithelial airway ET-1 levels contribute to the anaphylactic reaction of guinea pig airways.