Summary
Prostaglandins (PG) E2 and I2 have a number of effects on renal function, such as causing vasodilatation, increasing the glomerular filtration rate, sodium chloride excretion, water excretion, and stimulating renin secretion. Studies in dogs have shown that reductions in renal blood flow associated with angiotensin II administration are accompanied by increased synthesis of vasodilatory PGE2 followed by a compensatory increase in blood flow. Moreover, in rats and dogs, non-steroidal anti-inflammatory drugs (NSAIDs) markedly augment the reductions in renal blood flow associated with angiotensin II administration. Clinical use of NSAIDs can induce 1 of 2 types of renal syndromes in patients with certain predisposing conditions. These syndromes are ischaemic acute renal failure and papillary necrosis or, rarely, an idiosyncratic reaction. It is believed that the effects of cyclo-oxygenase inhibitors on renal function are most important in patients with these predisposing conditions because in many of these conditions there is increased synthesis of renal PGE2 and PGI2 to compensate for abnormally high plasma concentrations of vasoconstrictor hormones.
Angiotensin II produces a concentration-dependent contraction of isoluted rat glomeruli or mesangial cells which is potentiated by pretreatment with indomethacin or meclofenamate. Pretreatment with arachidonic acid, or addition of exogenous PGE2, inhibits the angiotensinmediated glomerular contraction. Stable endoperoxide analogues, which mimic the effects of thromboxane A2, induce a similar glomerular contraction to angiotensin. Similar findings were recorded using isolated rat mesangial cells. Mesangial cell contraction is believed to reduce the filtration surface area of the glomerulus and, therefore, the glomerular filtration rate. In these cells angiotensin II not only induces contraction but also increases the rate of synthesis of PGE2.
Associated with the acute reduction in renal function after induction of an immune glomerular nephritis in rats, there is a marked increase in glomerular thromboxane synthesis. The thromboxane synthetase inhibitor dazoxiben inhibits this increase and prevents the acute renal changes which occur in untreated animals during the first 3 hours after antibody injection. However, thromboxane synthetase inhibitors have no influence on renal function when nephrotoxic serum nephritis has been establised for 14 days.
In conclusion, maintenance of adequate renal function would seem to be dependent on a balance of substances causing mesangial relaxation (PGE2 and PGI2) and contraction (thromboxanes, endoperoxides and leukotrienes). In certain disease states this balance is upset and there is a compensatory increase in prostaglandin synthesis. Patients with such conditions may be at particular risk of developing renal toxicity if treated with NSAIDs.
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Dunn, M.J. The Role of Arachidonic Acid Metabolites in Renal Homeostasis. Drugs 33 (Suppl 1), 56–66 (1987). https://doi.org/10.2165/00003495-198700331-00009
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DOI: https://doi.org/10.2165/00003495-198700331-00009