title: [Polyunsaturated fatty acid biogenesis is impaired in spontaneously hypertensive rat in relation to the pathogenesis of hypertension].
abstract: This study was designed to investigate polyunsaturated fatty acid (PUFA) biogenesis in spontaneously hypertensive rats (SHR) during the onset of hypertension. We measured liver desaturase activities, limiting enzymes of linoleic (LA) biosynthesis into arachidonic acid (AA). Fifteen male SHR and 15 male Wistar Kyoto (WKY) normotensive rats were killed at 7.9 or 13 week-old (5 per group). Systolic blood pressure was measured by plethysmography. Liver microsomes were obtained after ultracentrifugation and 5 mg of microsomal proteins incubated during 5 minutes at 37 degrees C with 0.04 mumoles of (1-14C) LA or (2-14C) dihomo-gamma-linolenic acid (DGLA). After fatty acid saponification and methylation, the bioconversion of (1-14C) LA into (1-14C) gamma-linolenic acid (GLA; delta 6 desaturation) and of (2-14C) DGLA into (2-14C) AA (delta 5 desaturation) was determined by measuring the radioactivity shared out between substrate and product of desaturation, after HPLC partition. Fatty acid composition of liver total lipids was calculated after GLC partition. In 7 week-old SHR, blood pressure was closed to that of WKY rats, higher in the 9 week-olds, when hypertension was settled in the 13 week-olds. Delta 6 and delta 5 desaturase activities were lower in SHR than in corresponding WKY. Those impaired desaturase activities increased with the age of rats: delta 6 desaturase activity was 43, 70 and 61% lower in the 7, 9 and 13 week-old SHR, respectively; delta 5 desaturase activity was 14, 48 and 53% lower in the same conditions. We observed a liver storage of total lipids in the 3 groups of SHR. The fatty acid composition of liver total lipids shows a lower proportion of AA and a higher proportion of LA in SHR than in WKY rats, confirming the depletion of the enzymatic systems studied. In summary, LA bioconversion into AA is decreased in liver microsomes of SHR, via the desaturase impairments. This phenomenon is concomitant with the pathogenesis of hypertension and related to the liver fatty acid composition. Such results explain partly the effects of PUFA rich diets administered to hypertensive rats, and clarify the interpretation of such effects.
authors.affiliation: Unité de nutrition cellulaire et métabolique, EA DGRT 1867, Université de Bourgogne, Dijon.
authors.forename: M
authors.initials: M
authors.lastname: Narce
authors.forename: J P
authors.initials: JP
authors.lastname: Poisson
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001835:Body Weight; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D006973:Hypertension / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D008055:Lipids; D016718:Arachidonic Acid; D019787:Linoleic Acid; D044943:Fatty Acid Desaturases
vernacular_title: La biogenèse des acides gras polyinsaturés est altérée chez le rat spontanément hypertendu lors de l'installation de l'hypertension artérielle.