TISSUE ANGIOTENSINOGEN GENE-EXPRESSION INDUCED BY LIPOPOLYSACCHARIDE IN HYPERTENSIVE RATS

There is now convincing evidence that various tissues express their ow n tissue renin-angiotensin system, which may be regulated independentl y of the systemic renin-angiotensin system. However, little informatio n is available on the regulation of the tissue renin-angiotensin syste m. We investigated the regulation of tissue angiotensinogen gene expre ssion with respect to the development of hypertension. We measured bas al and lipopolysaccharide-stimulated plasma angiotensinogen concentrat ions by radioimmunoassay and examined the expression of tissue angiote nsinogen by Northern blot analysis in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at 4 and 13 weeks of age. Basal plas ma angiotensinogen concentration in SHR was comparable to that in WKY at 4 weeks of age and was significantly higher than that in WKY at 13 weeks of age. Lipopolysaccharide induced a significant increase in pla sma angiotensinogen concentration in both WKY and SHR at 4 and 13 week s of age. At 4 weeks of age, the basal levels of angiotensinogen mRNA in the liver, fat, adrenal, and aorta were higher in WKY than in SHR. At 13 weeks of age, the basal levels of angiotensinogen mRNA in the fa t, adrenal, aorta, spleen, and kidney were higher in WKY than in SHR, while that in the liver did not differ significantly between the two s trains. At 4 weeks of age, pretreatment with lipopolysaccharide increa sed the angiotensinogen mRNA levels in the liver, fat, adrenal, and ao rta in both WKY and SHR. At 13 weeks of age, pretreatment with lipopol ysaccharide increased the angiotensinogen mRNA levels in the liver, ao rta, and adrenal; decreased those in the spleen; and had no effect in the kidney in both WKY and SHR. Interestingly, lipopolysaccharide incr eased the angiotensinogen mRNA level in fat only in SHR, with no effec t in WKY, at 13 weeks of age. Lipopolysaccharide stimulated tumor necr osis factor-alpha mRNA expression in fat of WKY and SHR, and the incre ase in tumor necrosis factor-alpha mRNA level in SHR was significantly greater than that in WKY. Therefore, the increased tumor necrosis fac tor-alpha mRNA expression may be involved in the increased lipopolysac charide-induced expression of angiotensinogen gene in fat of SHR at 13 weeks of age. These data suggest that the transcriptional and probabl y posttranscriptional regulation of angiotensinogen mRNA differs betwe en SHR and WKY, that the regulation of angiotensinogen gene expression is tissue-specific, and that the altered expression of the angiotensi nogen gene may be involved in the development of hypertension.