Peroxisome Proliferator-Activated Receptor Gamma(PPAR-gamma) Agonist Improves Endothelial Function in Diabetic Patients with Metabolic Syndrome: Pivotal Role of NOx and Inflammation

BACKGROUND AND OBJECTIVES: Nitric oxide (NO) is thought to have antiatherosclerotic properties. On the other hand, NO activity is reduced in patients with metabolic syndrome, and endothelial dysfunction is an important early sign of atherosclerosis in patients with metabolic syndrome. The aim of this study was to investigate the effect of pioglitazone on the endothelial function in terms of the plasma NOx (combined nitrate/nitrite), the circulating inflammatory markers and the autonomic nervous system. SUBJECTS AND METHODS: We randomized 40 subjects with metabolic syndrome, and they were assigned to receive 15 mg of pioglitazone per day (the PIO group, n=21) during 12 weeks or they were placed in the placebo group (the PLA group, n=19). We estimate the endothelial function by performing vascular ultrasound. The plasma NOx levels, the levels of the inflammatory markers and the GRK2 levels were measured. RESULTS: After 12 weeks of therapy, flow mediated dilation (FMD) was improved in the PIO group (from 6.7+/-6% to 11.7+/-5%, respectively: p<0.05), but not in the PLA group. The level of plasma NOx was increased in the PIO group (from 67.7+/-30 nmol/dL to 92.9+/-41 nmol/dL, respectively: p<0.001), but not in the PLA group. The plasma levels of hsCRP and IL-6 dropped significantly (from 2.6+/-2.3 mg/L to 1.2+/-1.3 mg/L and 1.7+/-2.1 pg/mL to 0.7+/-0.5 pg/mL, respectively: p<0.05) in the PIO group, but not in the PLA group. The levels of GRK2 (the PLA group from 0.0061+/-0.0023 ng to 0.0075+/-0.0031 ng, and the PIO group from 0.0024+/-0.002 ng to 0.0015+/-0.001 ng, p=ns) didn't dropped significantly. CONCLUSION: Administration of PPAR-gamma agonist in patients suffering with metabolic syndrome improves their endothelial function, enhances the production of NOx and reduces the proinflammatory markers, but this is not related to sympathetic regulation. PPAR-gamma agonist may be able to modulate the progression of atherosclerosis.

Role of vascular mediators in the pathogenesis of hepatopulmonary syndrome in rats / 中国普通外科杂志

Objective To study the role of vascular mediators in the pathogenesis of hepatopulmonary syndrome in rats. Methods Male Sprague-Dawley (SD) rats were divided into four groups: SO (surgical control), IHPH (intrahepatic portal hypertension), PHPH (prehepatic) and PCS (portocaval shunt). Two weeks after pathological study, arterial blood gas and the concentrations of NO, glucagon, VIP and ET-1 in plasma and lung were determined. Results Lung structural alteration of rats induced by CCl 4 was of alveolar capillary dilation and angiogenesis, thickened alveolar septa and decreased alveolar capacity. There was no inflammation, edema, fibrosis, alveolar collapse and hyaline membrane formation in lung of all rats. PaO 2 ( mm?Hg)decreased more significantly in IHPH (73.85?6.51) rats than in PHPH (972?9?1.33), PCS (95.23?2.22) and SO rats (99.05?0.75). The level of lung NO of IHPH (19.78?5.33) was significantly increased than those of PHPH (13.21?3.99) and PCS (13.89?3.16) whose level in lung homogenate increased than those of SO (8.71?1.68). There was no difference of Glu and VIP levels in lung among all rats. The level of lung ET-1 in IHPH was significantly decreased than other rats. Conclusion Increased NO levels and decreased ET-1 levels in lung of HPS rats cause alveolar dilation and angiogenesis leading to mismatched ventilation-perfusion, and decrease of PaO 2.