CHANGES IN GENE-EXPRESSION OF THE RENIN-ANGIOTENSIN SYSTEM IN 2-KIDNEY, ONE CLIP HYPERTENSIVE RATS

To investigate the molecular mechanism of sustained hypertension in two-kidney, one clip (2K1C) hypertensive rats, possible changes in renin gene expression in the kidney and angiotensinogen in the liver were studied. In 2K1C rats 4 weeks after clipping, the plasma renin and angiotensin II levels were significantly higher than those in sham-operated rats, but the plasma angiotensinogen level were similar in the two groups. At this time, expression of the renin gene in the ischaemic kidney of 2K1C rats was 2.6-times that in sham-operated rats P < 0.05), but expressions of the angiotensinogen gene were similar in the two groups. Sixteen weeks after clipping, the plasma renin and angiotensin II levels in 2K1C rats were not significantly higher than those in sham-operated controls, but expression of the renin gene in the kidney was still 2.2-times higher in 2K1C rats than in controls (P < 0.05). The plasma angiotensinogen level was significantly higher in 2K1C rats than in controls (P < 0.05), and expression of the angiotensinogen gene in the liver was 2.9-times higher in 2K1C rats than in controls (P < 0.01). These results indicate that the roles of the renin-angiotensin system in maintenance of hypertension in 2K1C rats differ in the acute and chronic phases: in the acute phase, over-expression of the renal renin gene coupled to increased renin secretion plays the major role in elevating the blood pressure; in the chronic phase, a counter-regulatory mechanism may affect the post-transcriptional fate of renin. Consistent over-expression of the renin gene and mobilization of the angiotensinogen gene, i.e. over-expression of the renin-angiotensin system, may contribute to the maintenance of hypertension.