title: Renal sodium handling and stimulation of medullary Na-K-ATPase during blockade of prostaglandin synthesis.
abstract: 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 normal 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 less than 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, 0.1 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 less than 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 x 10(-11) mol/mm/min (p less than 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.
authors.affiliation: Neprhology Services, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Rubinger
authors.forename: H
authors.initials: H
authors.lastname: Wald
authors.forename: P
authors.initials: P
authors.lastname: Scherzer
authors.forename: M M
authors.initials: MM
authors.lastname: Popovtzer
mesh_terms: D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007679:Kidney Medulla / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D009318:Natriuresis / Q000187:drug effects; D011453:Prostaglandins / Q000096:biosynthesis*; D011454:Prostaglandins A / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D012982:Sodium, Dietary / Q000008:administration & dosage; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D011453:Prostaglandins; D011454:Prostaglandins A; D012982:Sodium, Dietary; D012964:Sodium; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase; C100008:prostaglandin A2; D015232:Dinoprostone; D007213:Indomethacin