DIFFERENCES IN THE METABOLISM OF 18 2N-6 AND 18/3N-6 BY THE LIVER ANDKIDNEY MAY EXPLAIN THE ANTIHYPERTENSIVE EFFECT OF 18/3N-6/

The present study examined the in vitro and in vivo metabolism of 18:2 n-6 and 18:3n 6 by kidney and liver in the male adult spontaneously hy pertensive (SHR) and normotensive (WKY) rats. In liver and kidney slic es incubated for 1 h with either [1-C-14]18:2n-6 or [1-C-14]18:3n-6 (6 0 mu M), substantial amounts of radioactivity were incorporated into t riacylglycerol and phospholipid fractions. Approximately 15% of the ra diolabeled 18:2n 6 was converted into 18:3n-6 in liver slices but no c onversion was found in kidney slices. When incubated with radiolabeled 18:3n-6, over 40% of the radioactivity was metabolized mainly to 20:4 n-6 in liver slices, but evenly to 20:3n-6 and 20:4n-6 in kidney slice s. There were no differences between the results from SHR and those fr om WKY. In WKY rats given an oral bolus of radiolabeled 18:3n-6, most of the radioactivity was recovered in the liver and significantly less in the kidney. In both tissues, the radioactivity was associated init ially only with 18:3n 6 and later with its elongation product, 20:3n-6 . These findings indicated that the kidney, although unable to metabol ize 18:2n 6, could metabolize 18:3n 6 taken up from the circulation. T he effectiveness of 18:3n 6, compared to 18:2n-6, as an anti hypertens ive agent may result from the provision of a post-Delta 6-desaturation metabolite which can be directly converted to blood pressure-regulati ng eicosanoids in the kidney. (C) 1994 Academic Press, Inc.