Consistent activation of prorenin mRNA in renal hypertensive rats.

To investigate the mechanism of maintaining hypertension in chronic two-kidney, one-clip (2K1C) rats, we studied the expression of the kidney renin gene. Total cellular RNA was extracted by the guanidine thiocyanate--CsCl method. Kidney renin messenger RNA was quantified by densitometric Northern blot analysis using 32P-labeled rat renin genomic DNA as a hybridization probe. Sixteen weeks after clipping, plasma renin concentration and plasma angiotensin II concentration did not differ between 2K1C and sham-operated rats (plasma renin activity, sham rats 16.2 +/- 4.2 vs. 2K1C rats 8.9 +/- 1.3 ng angiotensin I.mL-1.h-1; plasma angiotensin II, sham rats 14.7 +/- 7.5 vs. 2K1C rats 6.8 +/- 1.3 pg/mL), while plasma angiotensin concentration in 2K1C rats was higher than that of sham rats (p less than 0.05). Renin gene expression in the ischemic kidney was 2.2 times higher than that in the kidney of sham-operated rats (p less than 0.05), and decreased to 80% of those in the kidneys of sham-operated rats. These results suggest that overexpression of the kidney renin gene in the chronic phases of 2K1C rats may contribute to the sustained high blood pressure, and the kidney renin gene may be inhibited by posttranscriptional factors, i.e., suppressed activation of prorenin to renin.