Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hilltop (H) and Madison (M) strains of Sprague-Dawley rats exhibit strikingly different susceptibilities to the effects of chronic altitude exposure. The H rats develop greater polycythemia, hypoxemia, and pulmonary hypertension. We studied ventilation, pulmonary gas exchange, tissue oxygenation, and hematologic adaptations in the two rat strains during a 50-day exposure to a simulated altitude (HA) of 5,500 m (18,000 ft). There were no strain differences among the variables we studied under sea level (SL) conditions. Within the first 14 days of hypoxic exposure, the only significant strain differences were that erythropoietin (EPO) rose much higher and erythroid activity was greater in the H rats, even though arterial Po2 and PCo2 (Pao2 and PaCo2, respectively), renal venous PO2 (Prvo2), and ventilation (VE) were equivalent in the two strains during this time. By day 14 at HA, the H rats had significantly higher erythroid activity, hematocrit (Hct), and EPO levels, significantly lower PaO2 and PrvO2, but equivalent VE and PaCO2. These changes persisted for the remainder of the exposure, except that the Hct continued to rise and the increase was greater in H rats. Despite the greater O2-carrying capacity of H rats in the later stages of hypoxic exposure, PaO2 and PrvO2 were significantly lower in H rats. There were no strain differences at either SL or HA in ventilatory responses to hypercapnia or hypoxia, in blood O2 affinity or 2,3-diphosphoglycerate, in extrarenal production of EPO, or in EPO clearance. We conclude that early in the hypoxic exposure the H rats produce more EPO at apparently equivalent levels of hypoxia, and this is the first step in the pathogenesis of the maladaptation to HA manifest by H rats. We find no consistent evidence that differences in VE contribute to the variable susceptibility to hypoxia in the two rat strains.
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PMID:Ventilatory and hematopoietic responses to chronic hypoxia in two rat strains. 162 91

Recent evidence indicates the existence of a protein related to the erythroid chloride-bicarbonate exchanger (band 3 protein) in the basolateral aspect of type A intercalated cells of the distal nephron. To probe the possible participation of this transporter in the renal adaptation to chronic hypercapnia, we examined the steady-state abundance of band 3 mRNA in the kidney during respiratory acidosis of variable duration. Total RNA was isolated from renal cortex and medulla of rats maintained in a 10% CO2 atmosphere for 2 or 5 days and from contemporaneous controls. The RNA was analyzed by Northern blot assay using cDNA probes for band 3 and beta-actin genes. Using a 3' cDNA probe encoding the membrane-associated domain of band 3 protein that is involved in anion exchange, we found a two- to threefold increase in steady-state mRNA levels (whether or not correction for the beta-actin signals was applied) in renal cortex and medulla at 5 days of hypercapnia. Similar, but less definitive, increases were observed at the 2-day time point. Using a 5' cDNA probe encoding an erythroid-protein segment absent from the kidney band 3 major transcript, we detected meager hybridization in renal tissue and no measurable variation during hypercapnia. Use of splenic RNA as a positive control for the 5' probe disclosed marked reduction of band 3 mRNA levels in hypercapnia, indicating organ specificity of band 3 gene expression. We conclude that steady-state levels of kidney band 3 mRNA increase in chronic respiratory acidosis as a result of transcriptional or posttranscriptional regulatory mechanisms. This adaptation might be involved in the augmentation of renal acidification characteristic of chronic hypercapnia.
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PMID:Rat kidney band 3 mRNA modulation in chronic respiratory acidosis. 199 72