ABSTRACT
INTRODUCTION: Vascular smooth muscle cells (VSMCs) are essential for maintaining vasculature homeostasis and function. By influence on its growth and activation both proinflammatory cytokines and peptides of the renin-angiotensin system (RAS) are potent regulators of VSMCs. Interestingly, angiotensin (Ang) II and Ang-(1-7) elicit opposite effects on VSMC activation, differentiation and proliferation. It has been suggested that statins, besides anti-inflammatory effects, may also modulate VSMC activation by their influence on the RAS. METHODS: The effect of atorvastatin on Ang I metabolism in a culture of explanted rat VSMCs was examined by liquid chromatography-mass spectrometry (LC-MS); expression of mRNA of the main RAS enzymes in VSMC was assessed by real-time polymerase chain reaction (PCR). RESULTS: In VSMC culture Ang-(1-7) was identified as a major product of Ang I metabolism. In this setting, TNF-α (1 ng/ml) caused a decrease in the conversion of Ang I to Ang-(1-7). This effect was accompanied by a decrease of mRNA expression of neutral endopeptidase (NEP) and angiotensin converting enzyme 2 (ACE2) and increase of mRNA of ACE. Interestingly, atorvastatin (3 µM) attenuated the effects of TNF-α on Ang-(1-7) production as well as reversed the influence of TNF-α on ACE and ACE2 expression. CONCLUSIONS: Enhancement by atorvastatin of the ACE2/Ang-(1-7) axis in VSMCs could represent a new and beneficial mechanism on cardiovascular action of this widely used drug.
Subject(s)
Angiotensin I/metabolism , Heptanoic Acids/pharmacology , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/metabolism , Pyrroles/pharmacology , Tumor Necrosis Factor-alpha/pharmacology , Angiotensin-Converting Enzyme 2 , Animals , Atorvastatin , Myocytes, Smooth Muscle/drug effects , Neprilysin/metabolism , Peptidyl-Dipeptidase A/metabolism , Rats, Wistar , RestABSTRACT
The main aim of this study was to examine the role of lipopolysaccharide (LPS) and hypoxia on respiratory burst in rat neutrophils in vitro. Hypoxia (2% oxygen tension) inhibited respiratory burst of neutrophils in response to phorbol ester. Neutrophils treatment by LPS and hypoxia resulted in significant augmentation respiratory burst via NADPH oxidase activity in luminol chemiluminescence. This paper suggests that induction of iNOS was responsible for this effect.
Subject(s)
Lipopolysaccharides/metabolism , Neutrophils/metabolism , Respiratory Burst/physiology , Animals , Cell Hypoxia , Lipopolysaccharides/pharmacology , Luminescent Measurements , NADPH Oxidases/metabolism , Neutrophils/drug effects , Oxygen Consumption/drug effects , Oxygen Consumption/physiology , Rats , Rats, Wistar , Respiratory Burst/drug effectsABSTRACT
The objective of the present study was to investigate the effect of beta2-adrenoreceptor polymorphisms Arg16Gly and Gln27Glu as well as their relationship to the pulmonary function parameters, and the clinical presentation in patients with asthma and allergic rhinitis. Investigated polymorphisms were in linkage disequilibrium, therefore their effects should be evaluated collectively. Although no significant association could be found with the presence of asthma or allergic rhinitis in studied population, polymorphisms of beta2-adrenoreceptor can influence pulmonary function in these patients. These effects significantly differ between men and women, possibly indicating the effect of sex hormones on genetic regulation of pulmonary function.