Effects of sodium depletion on renal prostanoid synthesis in rats: influence of the converting enzyme inhibitor captopril.
1. The synthesis of prostaglandin (PG) E2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane (TX) B2 by isolated glomeruli, cortical tubules, inner medullary slices and outer medullary slices was measured in salt-depleted (LNa) rats and in salt-depleted rats receiving captopril (LNa-CEI). Animals were studied before and after 4, 9 and 15 days of Na+ depletion. 2. Na+ balance was reached in LNa rats after 4 days. Blood pressure and creatinine clearance remained stable. Serum Na+ decreased from 140 +/- 1 to 126 +/- 1 mmol/l (mean +/- SEM, P less than 0.01). In contrast, LNa-CEI rats were unable to conserve Na+ adequately: fractional excretion of Na+ and natriuresis were constantly greater than in LNa animals. As a consequence, LNa-CEI rats developed severe hyponatraemia, lost weight and their creatinine clearance decreased. 3. The glomerular synthesis of PGE2, PGF2 alpha and 6-keto-PGF1 alpha, but not of TXB2, was significantly increased in LNa rats. In LNa-CEI rats, the synthesis of PGE2 and 6-keto-PGF1 alpha was similar to control values, but PGF2 alpha and TXB2 synthesis was elevated at day 9. In cortical tubules, PGE2 and PGF2 alpha were unaffected by Na+ depletion, but 6-keto-PGF1 alpha and TXB2 were increased and a similar trend was observed in LNa-CEI rats. In outer medulla of LNa rats, a decrease in all the eicosanoids measured was observed at day 4. In LNa-CEI animals, the synthesis of PGE2 and PGF2 alpha, but not of 6-keto-PGF1 alpha and TXB2, was significantly depressed. In inner medulla, Na+ depletion only tended to decrease PGF2 alpha and 6-keto-PGF1 alpha, but in the presence of captopril, the synthesis of all prostanoids was significantly decreased.
Rathaus
M
M
Department of Nephrology, Meir Hospital, Kfar Saba, Israel.
Podjarny
E
E
Pomeranz
A
A
Shapira
J
J
Kariv
N
N
Bernheim
J
J
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D012898:Autacoids / Q000096:biosynthesis*; D002216:Captopril / Q000494:pharmacology*; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000172:deficiency* / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis
D012898:Autacoids; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D002216:Captopril; D012964:Sodium; D015237:Dinoprost; D015232:Dinoprostone