Differences in the metabolism of 18:2n-6 and 18:3n-6 by the liver and kidney may explain the anti-hypertensive effect of 18:3n-6.
The present study examined the in vitro and in vivo metabolism of 18:2n-6 and 18:3n-6 by kidney and liver in the male adult spontaneously hypertensive (SHR) and normotensive (WKY) rats. In liver and kidney slices incubated for 1 h with either [1-14C]18:2n-6 or [1-14C]18:3n-6 (60 microM), substantial amounts of radioactivity were incorporated into triacylglycerol and phospholipid fractions. Approximately 15% of the radiolabeled 18:2n-6 was converted into 18:3n-6 in liver slices but no conversion was found in kidney slices. When incubated with radiolabeled 18:3n-6, over 40% of the radioactivity was metabolized mainly to 20:4n-6 in liver slices, but evenly to 20:3n-6 and 20:4n-6 in kidney slices. There were no differences between the results from SHR and those from 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 initially only with 18:3n-6 and later with its elongation product, 20:3n-6. These findings indicated that the kidney, although unable to metabolize 18:2n-6, could metabolize 18:3n-6 taken up from the circulation. The effectiveness of 18:3n-6, compared to 18:2n-6, as an anti-hypertensive agent may result from the provision of a post-delta 6-desaturation metabolite which can be directly converted to blood pressure-regulating eicosanoids in the kidney.
Huang
Y S
YS
Efamol Research Institute, Kentville, Nova Scotia, Canada.
Cantrill
R C
RC
DeMarco
A
A
Campbell
L
L
Lin
X
X
Horrobin
D F
DF
Mills
D E
DE
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002250:Carbon Radioisotopes; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000378:metabolism* / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017962:alpha-Linolenic Acid / Q000378:metabolism / Q000494:pharmacology
D000959:Antihypertensive Agents; D002250:Carbon Radioisotopes; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D008055:Lipids; D017962:alpha-Linolenic Acid; D019787:Linoleic Acid