losartan-potassium and Acidosis--Respiratory

Acetazolamide has been recognized as an effective treatment for acute mountain sickness. The efficacy of acetazolamide is related to metabolic acidosis, which promotes chemoreceptors to respond to hypoxic stimuli at altitude. In this study, adult male Sprague-Dawley rats were treated with acetazolamide (100mg/kg or 50mg/kg, I.P.) for 3 days. Primary cultured cortical neurons and PC12 cell lines were exposed to acidosis-permissive (pH 6.5) or standard (pH 7.2) media for 20h. HIF-1alpha and its target genes were assayed by Western blot, real-time PCR, HIF-1 DNA-binding assay and chloramphenicol acetyltransferase reporter gene assay. HIF-1alpha protein level and HIF-1 DNA-binding activities were increased in cerebral cortices of rats treated with acetazolamide. Moreover, the mRNA levels of erythropoietin, vascular endothelial growth factor, and glucose transporter-1 also increased. The HIF-1alpha protein level and activity of HIF-driven chloramphenicol acetyltransferase reporters of cortical neurons and PC12 cells treated with acidosis media were significantly enhanced. We conclude that the normoxic induction of HIF-1alpha and HIF-1 mediated genes by acetazolamide may mediate the effect of acetazolamide in the reduction of symptoms of acute mountain sickness.

Topics: Acetazolamide; Acidosis, Respiratory; Altitude Sickness; Animals; Carbonic Anhydrase Inhibitors; Cells, Cultured; Cerebral Cortex; Disease Models, Animal; DNA-Binding Proteins; Erythropoietin; Glucose Transporter Type 1; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Oxygen; PC12 Cells; Rats; Rats, Sprague-Dawley; RNA, Messenger; Up-Regulation; Vascular Endothelial Growth Factor A

Erythropoietin (EPO) production in response to hypoxic hypoxia is known to be attenuated by simultaneous hypercapnia. This study aimed to investigate whether this inhibitory effect of hypercapnia is 1) a direct effect of carbon dioxide or mediated by changes in pH or bicarbonate, 2) affects also carbon monoxide hypoxia, and 3) influences either the synthesis and release of EPO or the mechanisms by which hypoxia triggers an increase in EPO production rate. We found that EPO formation in mice exposed to normobaric hypoxia (8% O2) or to carbon monoxide (0.1%) was reduced by 30 and 42% when animals were simultaneously exposed to hypercapnia (7% CO2), by 35 and 38% when subjected to metabolic acidosis (NH4Cl), and unchanged when subjected to metabolic alkalosis (NaHCO3). In animals exposed to brief hypoxia (15 min) and subsequent normoxia (2 h), metabolic acidosis did not affect EPO levels when initiated after the hypoxic period. The results indicate that acidosis inhibits hypoxia-induced triggering of EPO formation independently of PCO2 and HCO3 levels. Because this inhibitory effect is also present during carbon monoxide hypoxia, it appears not solely due to potentiated hyperpnea. Alternatively, it may result from a facilitated intrarenal oxygen release or a direct effect at the EPO production sites.

Topics: Acid-Base Equilibrium; Acidosis; Acidosis, Respiratory; Animals; Carbon Monoxide; Erythropoietin; Hydrogen-Ion Concentration; Hypoxia; Male; Mice

In a survey the correlations between hypoxia, acidosis and nephrology are presented. In chronic oxygen deficiency the individual aspects concern the uncertainties of erythropoietin and the carotid-sinusoidal natriuresis stimulated by chemoreceptors. The effects of acute ischaemic hypoxic reactions are described with regard to the acute renal failure. The regulatory renal function of acidification and its disturbance in chronic renal insufficiency as well as the renotubular acidosis are discussed. Finally the authors enter the influence on the renal function during positive pressure respiration (e.g. for the purpose of the normalisation of the pulmonary gas exchange in acute respiratory insufficiency) as well as on reactions of the haemodialysis (bicarbonate and acetate dialysis) to the blood gas and acid-base metabolism, taking into consideration the pulmonary function.

Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Acidosis, Respiratory; Acute Kidney Injury; Erythropoietin; Glomerular Filtration Rate; Humans; Hypercapnia; Hypoxia; Kidney; Kidney Tubules; Natriuresis; Positive-Pressure Respiration; Renal Dialysis