The effect of prostaglandin synthesis inhibitors on sodium excretion in the awake rat during acute water and isotonic Ringer loading.

Studies were performed to determine the effect of decreased endogenous release of renal prostaglandins on urinary sodium excretion. Two structurally different inhibitors of prostaglandin synthesis were employed and studies were performed in conscious rats allowed to recover from prior surgical instrumentation. Either meclofenamate (5 mg/kg) or indomethacin (5 mg/kg) was given to unanesthetized rats undergoing either a saline diuresis (n = 24, group A) or a water diuresis (n = 27, group B). In a third group (n = 27, group C) the drugs were given during hydropenia at the onset of a massive volume expansion (10% BW over 60 min). GFR, PAH clearance, absolute (UNaV) and fractional sodium excretion (FENa) and urinary prostaglandin E2 and F2 alpha excretion were measured, after prostaglandin inhibitor or placebo injections. In group A, renal function and UNaV or FENa were not altered by indomethacin or placebo injection despite a 50% fall in both UPGE2 and UPGF2 alpha excretion after prostaglandin inhibitors. Meclofenamate produced a fall in PAH clearance from 27.0 to 21.2 ml/min. kg with a decrease in UNa V from 64.7 to 44.3 microEq/min, kg (p < 0.05). In group B, the administration of either prostaglandin inhibitors or placebo did not alter GFR, PAH clearance, UNa V or FENa despite a decrease in UPG excretion with 48% after PG inhibitors. In group C, the rise in FENa after acute volume expansion was similar in prostaglandin inhibited rats compared to placebo injected animals (delta FENa was 6.67% after placebo, 5.85% after meclofenamate and 6.03% after indomethacin, respetively; p > 0.05). However, both meclofenamate and indomethacin adminsitration blunted the rise in GFR, PAH clearance, UPGE2 and UPGF2 alpha excretion normally observed during volume expansion in the placebo injected rats. Thus, these findings seem to indicate that endogenous intrarenal prostaglandins are not important determinants of the natriuretic response to an acute expansion of the extracellular volume. They do not give persuasive evidence that renal praostaglandin production and renal sodium excretion are closely interrelated or interdependent.