Biomedical subjects
C Gleiter
Publications and source records attributed to C Gleiter.
Therapeutic use of theophylline to antagonize renal effects of adenosine.
Experiments in laboratory animals clearly show that adenosine acts as a vasoconstrictive metabolite in the kidney. Adenosine receptor antagonists like theophylline can inhibit renal vasoconstriction in response to exogenous and endogenous adenosine. Based on these findings a number of experiments have been performed to test whether the vasoconstrictive action of adenosine in the kidney might be important also in pathophysiological states. In various animal models theophylline and other methylxanthine derivatives have been successfully employed to improve renal function after induction of acute renal failure. Clinical implications of these experimental findings comprise the prevention of acute renal failure following the administration of radio contrast media by theophylline. Another therapeutic aspect derives from experimental and clinical data showing that theophylline controls erythropoietin production in erythrocytosis after renal transplantation.
[Hypernatremia and kidney function].
Hypernatremia is caused by a water deficit. Cases with hypernatremia and dehydration appear to cluster among children and the elderly with alterations in the level of consciousness thus with no independent access to water. In general, central nervous symptoms prevail. However, thorough examination reveals impaired renal function in many such cases. Animal experiments have shown that rapid increases of the sodium concentration in the renal artery will cause a reduction of renal blood flow (RBF), glomerular filtration rate (GFR) and inhibition of renin secretion, particularly during states of sodium chloride or volume depletion (i.e. with high plasma renin activity). In any other organ hypernatremia leads to vasodilation. The kidney, however, responds with vasoconstriction which can be reversed by the adenosine antagonist theophylline. This finding led to the hypothesis that adenosine mediates the renal response to hypernatremia. Adenosine is generated by the tubules at a higher rate when the kidney is forced to reabsorb large amounts of sodium. In this concept adenosine links metabolic processes of sodium reabsorption with the regulation of organ blood flow causing vasoconstriction via adenosine receptors on the vasa afferentia. This mechanism can explain impaired renal function during acute hypernatremia. It is concluded from experimental evidence that-apart from other therapeutic measures-the recovery of impaired renal function can be improved by administration of the adenosine antagonist theophylline.
[Renal effects of adenosine: possible consequences for kidney transplantation].
This review summarizes in the first part the action of adenosine on the kidney. In the second part we discuss the pathophysiological consequences and the possibilities of a pharmacological intervention to improve impaired kidney function. Adenosine causes vasoconstriction in the kidney and reduces glomerular filtration rate (GFR). This action is enhanced in proportion to elevated plasma renin activity. Chronic elevation of ureteral pressure enhances and reduction of renal perfusion pressure attenuates adenosine-induced vasoconstriction. From the kidney-specific relationship between renal blood flow and tubular electrolyte transport the concept is developed which ascribes adenosine a role of a mediator that is essentially contributing to the homeostatic regulation of kidney function. The accumulation of adenosine in the kidney tissue after ischemia or after administration of nephrotoxic substances led to the hypothesis that adenosine is an important intrarenal factor in the pathogenesis of acute renal failure. The possibility to antagonize adenosine actions in the kidney with theophylline was used successfully in a number of experimental studies in acute renal failure and most recently in a study in humans after contrast media administration. Adenosine actions mediated via membrane receptors must be separated from adenosine actions in the cell to increase ATP tissue content. The concept of the "University of Wisconsin" (UW) solution to improve the energy state of the tubular cells appears to be successful, however, we propose that the potential dangerous adenosine actions in the kidney, especially during the reperfusion phase may be antagonized by the administration of theophylline.