GENETIC-ANALYSIS OF RENIN GENE-EXPRESSION IN RAT ADRENAL-GLAND

We examined the mechanism of the increased renin mRNA concentration in the adrenal glands of spontaneously hypertensive rats (SHR). In 52 fe male F-2 rats (25 to 27 weeks of age) derived from SHR and Wistar-Kyot o rats, we determined blood pressure, renin mRNA concentration in the adrenal gland, plasma renin activity, plasma aldosterone concentration , and genotype of the renin gene. Eighteen of the F-2 rats were fed a high salt (8%) diet for 14 days. The renin mRNA concentration in the a drenal glands showed a significant correlation with the genotype of th e renin gene in the normal salt diet group (P<.0001), whereas this rel ationship was not observed in the high salt diet group. Multivariate a nalysis revealed that the plasma aldosterone concentration in the norm al diet group was significantly explained (P=.0004, R(2)=.454) by plas ma renin activity (P=.0005), the renin mRNA concentration in the adren al gland (P=.0496), and the genotype of the renin gene (P=.0236). The SHR allele of the renin gene was associated with a lower aldosterone c oncentration. On the other hand, in the high salt diet group, only the genotype of the renin gene showed a significant relationship with pla sma aldosterone concentration (P=.0237). Again, the SHR allele of the renin gene was associated with a lower aldosterone concentration. We c an conclude that the higher renin mRNA concentration in the SHR adrena l glands ii governed by the SHR allele of the renin gene or renin gene locus. The renin mRNA concentration in the adrenal gland exerts a min or influence on aldosterone synthesis. Paradoxically, the SHR allele o f the renin gene or renin gene locus confers a lower rate of aldostero ne synthesis at 25 to 27 weeks of age, the mechanism of which remains to be determined.