Prostaglandin synthesis and renal function in man.

Abstract

SUMMARY1. Experiments were performed to determine the changes in renal function which occur following prostaglandin synthetase inhibition in healthy conscious humans. It was hoped that such experiments could provide information on the mechanism by which renal prostaglandin synthesis influences urinary excretion.2. In water-diuretic male subjects (receiving a slow saline infusion) the renal excretion of sodium and water was reduced following i.v. acetylsalicylic acid (1 g) administration, while the effective renal plasma flow (p-aminohippurate clearance), and glomerular filtration rate (inulin clearance) remained unaltered. 3. In normally hydrated female subjects on an unrestricted diet, the mean urinary prostaglandin E output was 8-5 ng/hr. The renal excretion of sodium, water and urinary prostaglandin E were significantly reduced (P < 0.05) following oral acetylsalicylic acid (1 -2 g) administration.4. In normally hydrated female subjects on an unrestricted diet the renal excretion of sodium and water was reduced following oral paracetamol (1-5 g) administration.5. It is concluded that following renal prostaglandin synthetase inhibition in conscious humans, the excretion of sodium and water can be reduced without measurable changes in the glomerular filtration rate or effective renal plasma flow. It is suggested that in conscious healthy humans, the kidney may continually synthesize prostaglandin which might help to maintain sodium and water excretion by a direct action on the renal tubule without influencing renal blood flow. The relevance of this hypothesis to the intrarenal location of prostaglandin synthetase is discussed.

The comparative effects of paracetamol and indomethacin on renal function in healthy female volunteers.

“…Despite this wide use, very little is known of the acute effects of therapeutic doses of paracetamol on renal function. No information is available concerning its effects on renal prostaglandin synthesis in man but it has been reported to reduce sodium and water excretion (Haylor, 1980) and to have an antidiuretic effect in patients with diabetes insipidus (Nusynowitz & Forsham, 1966). In this report we describe the acute effects of paracetamol on renal prostaglandin synthesis, glomerular filtration rate, renal blood flow and renal function in healthy subjects under conditions of normal hydration and controlled sodium intake.…”

“…The effects of paracetamol on renal prostaglandins in man have not been described previously, but in animals it produces reversible, dose-dependent inhibition of renal medullary prostaglandin E2 synthesis by a direct action on cyclooxygenase without prior metabolic activation (Mattammal et al, 1979;Zenser et al, 1978). Haylor (1980) reported a reduction in urine volume, sodium excretion and osmolal output in six normally hydrated female subjects following administration of 1.5 g of paracetamol, but prostaglandins were not measured and the sodium intake was not controlled. In another report, paracetamol apparently reduced urine volume, urine osmolality and free water clearance in three patients with nephrogenic diabetes insipidus (Nusynowitz & Forsham, 1966).…”

Colchicine overdose with coingestion of nonsteroidal antiinflammatory drugs

“…The evidence suggests that indomethacin toxicity can result in ARF alone or in the presence of volume depletion. [23][24][25] One case described a 47-year-old man who suffered ARF postingestion of 20 mg (0.22 mg/kg) of colchicine with 600 mg of indomethacin. 26 ARF was attributed to the overdose of colchicine due to various factors, principally volume depletion.…”

Ramadan Fasting: Medical Aspects in Health and in Disease

“…Prostaglandins play a vital role in the control of hemodynamics and maintenance of renal function, especially in the presence of hypovolemia [19]. Non-steroidal anti-inflammatory drugs (NSAID), which are potent inhibitors of prostaglandins, might be expected to suppress renal perfusion and function during fasting.…”