Clinical and experimental pharmacology & physiology
-
Clin. Exp. Pharmacol. Physiol. · Oct 2006
ReviewRenal parenchymal oxygenation and hypoxia adaptation in acute kidney injury.
The pathogenesis of acute kidney injury (AKI), formally termed acute tubular necrosis, is complex and, phenotypically, may range from functional dysregulation without overt morphological features to literal tubular destruction. Hypoxia results from imbalanced oxygen supply and consumption. Increasing evidence supports the view that regional renal hypoxia occurs in AKI irrespective of the underlying condition, even under circumstances basically believed to reflect 'direct' tubulotoxicity. ⋯ Furthermore, renal parenchymal oxygen deprivation seems to participate in the pathogenesis of experimental AKI, induced by exogenous nephrotoxins (such as contrast media, non-steroidal anti-inflammatory drugs or amphotericin), sepsis, pigment and obstructive nephropathies. Sub-lethal cellular hypoxia engenders adaptational responses through hypoxia-inducible factors (HIF). Forthcoming technologies to modulate the HIF system form a novel potential therapeutic approach for AKI.
-
Clin. Exp. Pharmacol. Physiol. · Oct 2006
ReviewRenal oxygen delivery: matching delivery to metabolic demand.
The kidneys are second only to the heart in terms of O2 consumption; however, relative to other organs, the kidneys receive a very high blood flow and oxygen extraction in the healthy kidney is low. Despite low arterial-venous O2 extraction, the kidneys are particularly susceptible to hypoxic injury and much interest surrounds the role of renal hypoxia in the development and progression of both acute and chronic renal disease. ⋯ A number of such mechanisms specific to the kidney are reviewed herein, including the relationship between renal blood flow and O2 consumption, pre- and post-glomerular arterial-venous O2 shunting, tubulovascular cross-talk, the differential control of regional kidney blood flow and the tubuloglomerular feedback mechanism. The roles of these mechanisms in the control of renal oxygenation, as well as how dysfunction of these mechanisms may lead to renal hypoxia, are discussed.
-
Clin. Exp. Pharmacol. Physiol. · Oct 2006
ReviewHypoxia-induced erythropoietin production: a paradigm for oxygen-regulated gene expression.
The mechanisms controlling the expression of the gene encoding for the hormone erythropoietin (EPO) are exemplary for oxygen-regulated gene expression. In humans and other mammals, hypoxia modulates EPO levels by increasing expression of the EPO gene. An association between polycythaemia and people living at high altitudes was first reported more than 100 years ago. ⋯ In addition to erythropoiesis, HIF-1 regulates a broad range of physiologically relevant genes involved in angiogenesis, apoptosis, vasomotor control and energy metabolism. Therefore, the HIF system is implicated in the pathophysiology of many human diseases. In addition to the tight regulation by oxygen tension, temporal and tissue-specific signals limit expression of the EPO gene primarily to the fetal liver and the adult kidney.