POLYUNSATURATED FATTY-ACID BIOGENESIS IS IMPAIRED IN THE SPONTANEOUSLY HYPERTENSIVE RAT, IN RELATION TO THE PATHOGENESIS OF HYPERTENSION

This study was designed to investigate polyunsaturated fatty acid (PUF A) biogenesis in spontaneously hypertensive rats (SHR) during the onse t of hypertension, We measured liver desaturase activities, limiting e nzymes of linoleic (LA) biosynthesis into arachidonic acid (AA). Fifte en male SHR and 15 male Wistar Kyoto (WKY) normotensive rats were kill ed at 7, 9 or 13 week-old (5 per group). Systolic blood pressure was m easured by plethysmography. Liver microsomes were obtained after ultra centrifugation and 5: mg of microsomal proteins incubated during 5 min utes at 37 degrees C with 0.04 mu moles of (1-C-14) LA Or (2-C-14) dih omo-gamma-linolenic acid (DGLA). After fatty acid saponification and m ethylation, the bioconversion of (1-C-14) LA into (1-C-14) gamma-linol enic acid (GLA; Delta 6 desaturation) and of (2-C-14) DGLA into (2-C-1 4) AA (Delta 5 desaturation) was determined by measuring the radioacti vity shared out between substrate and product of desaturation, after H PLC partition. Fatty acid composition of liver total lipids was calcul ated 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 activites were lower in SHR than in corresponding WKY, Those impaired desaturas e activities increased with the age of rats : Delta 6 desaturase activ ity was 43, 70 and 61 % lower in the 7, 9 and 13 week-old SHR, respect ively; Delta 5 desaturase activity was 14, 48 and 53 % lower in the sa me conditions. We observed a liver storage of total lipids in the 3 gr oups 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 WK Y 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 wi th the pathogenesis of hypertension and related to the liver fatty aci d composition, Such results explain partly the effects of PUFA rich di ets administered to hypertensive rats, and clarify the interpretation of such effects.