Interaction of renal prostaglandins with the renin-angiotensin and renal adrenergic nervous systems in healthy subjects during dietary changes in sodium intake

Abstract

In six healthy subjects the role of renal prostaglandins (PG) in modulating the actions of the renin-angiotensin and renal adrenergic nervous systems on renal function was investigated. During high dietary sodium intake (350 mmol/day) for 4 days no changes in urinary excretion of PGE2, PGF2 alpha, noradrenaline or adrenaline were noted, whereas plasma renin activity (PRA) and urinary aldosterone excretion were suppressed. After 4 days of low sodium intake (35 mmol/day) urinary excretion of PGE2, aldosterone and noradrenaline, as well as PRA, had significantly increased. Inhibition of PG synthesis with indomethacin (2 mg/kg body weight) had no effects on renal function on day 5 of high sodium intake. Despite suppression of PRA and urinary aldosterone, indomethacin significantly reduced p-aminohippurate (PAH) clearance, glomerular filtration rate (GFR) and urinary sodium excretion on day 5 of low sodium intake, when urinary noradrenaline excretion remained high. The results point to the crucial role of the renal adrenergic nervous system in controlling renal vascular resistance and sodium conservation in healthy subjects during low sodium intake, which is unmasked when renal PG synthesis is blocked by indomethacin. Enhanced renal PG synthesis during sodium restriction therefore not only attenuates the vascular and tubular effects of the renin-angiotensin system but, more importantly, also those of the highly stimulated renal adrenergic nervous system.

The effects of ibuprofen and indomethacin on renal function in the presence and absence of frusemide in healthy volunteers on a restricted sodium diet.

“…In sodium restricted volunteers, glomerular filtration rate has been reduced (Donker et al, 1976) or unchanged (Roberts et al, 1985;Sedor et al, 1984) by indomethacin, which may also reduce (Kramer et al, 1985) or have no effect (Donker et al, 1976;Roberts et al, 1985;Sedor et al, 1984) on renal blood flow. In salt deplete volunteers indomethacin causes transient sodium retention (Donker et al, 1976;Roberts et al, 1985;Sedor et al, 1984).…”

“…In salt deplete humans, indomethacin has been reported to have little effect on basal renal haemodynamics (Donker et al, 1976;Mackay et al, 1984;Sedor et al, 1984), but there are reports of a significant decrease (Kramer et al, 1985). There is little information available on the renal haemodynamic effect of ibuprofen.…”

Distinct Role of Intrarenal Cyclooxygenase-1/2 in Chronic Unilateral Renal Ischemia

“…Teleologically, PG production is stimulated to counter the reduction in RBF in the face of renal ischemia [20]. In this circumstance, however, PG also affects renin release [7], which would subsequently elevate intrarenal Ang II production and might constitute a precipitating factor for the development of ischemic renal injury.…”

A comparison of the effects of ibuprofen and indomethacin upon renal haemodynamics and electrolyte excretion in the presence and absence of frusemide.

“…Ibuprofen is a proprionic acid derivative which is available without precription as an 'over the counter' preparation. In a salt replete situation in humans, indomethacin has little effect on renal haemodynamics (Rumpf et al, 1975;Donker et al, 1976;Epstein et al, 1979;Gullner et al, 1980;Kramer et al, 1985), but inhibits the acute changes induced by intravenous frusemide (Williamson et al, 1975;Mackay et al, 1984). There is little information available on the renal haemodynamic effects of ibuprofen.…”