Renal sodium handling and stimulation of medullary Na---K---ATPase during blockade of prostaglandin synthesis

The effect of suppression of prostaglandin synthesis on renal sodium handling and microsomal Na---K ATPase was studied in control and indomethacin treated intact rats maintained on a normal sodium diet (series A) and chronically salt loaded (series B). Indomethacin administration resulted in a decreased GFR and a significantly depressed urinary excretion and an increased fractional reabsorption of sodium in animals fed the normal sodium diet or chronically salt loaded. In rats maintained on a nomral Na diet, the activity of the renal medullary Na---K ATPase after indomethacin was 206.3±6.4 ug Pi./mg protein, i.e. significantly higher as compared with the enzyme activity in the medullary renal fraction from control animals in which it averaged 148±7.79 ug Pi/mg protein (p<0.001). While after chronic salt load a similar increment in the activity of renal medullary Na---K ATPase was observed, no additional stimulation was elicited by subsequent indomethacin administration. The addition of exogenous PGE₂, mM to microsomal fractions obtained from kidneys of normal rats, was associated with a moderate suppression of the medullary Na---K---ATPase activity, from a basal level of 170±16 to 151.3±13 umol Pi/mg protein/hr (p<0.005. In isolated segments of medullary thick ascending limb of Henle's loop (MTAL) addition of PGE₂ to the incubation medium resulted in a significant inhibition of Na---K--- ATPase from 37.2±2 to 21.25 ± 1.17 × 10⁻¹¹ mol/mm/min (p<0.0001.These findings suggest that the increased renal Na reabsorption after inhibition of PG synthesis might be related, at least partly, to stimulation of medullary Na---K ATPase. In parallel, the reported natriuretic effect of prostaglandins might imply a direct inhibitory effect of these mediators on renal Na---K ATPase.