INFLUENCE OF THE RENAL SYMPATHETIC-NERVES ON RENAL RENIN AND ANGIOTENSINOGEN GENE-EXPRESSION IN SPONTANEOUSLY HYPERTENSIVE RATS DURING DEVELOPMENT

Objective: To investigate the influence of renal sympathetic denervati on on renin and angiotensinogen gene expression in the kidney during g rowth and the development of hypertension in spontaneously hypertensiv e rats (SHR). Comparative studies were undertaken in age-matched normo tensive Wistar rats. Design: Four-week-old SHR and Wistar rats were su bjected to either denervation of the left kidney or sham operation. At age 5, 7 or 9 weeks the rats were lightly anaesthetized, carotid bloo d pressure was measured, a blood sample was taken and both kidneys wer e removed. Method: Plasma renin activity was measured by radioimmunoas say, and renal renin and angiotensinogen messenger RNA (mRNA) levels w ere measured by Northern blot hybridization followed by densitometric analysis. Results: In 5- and 7-week-old SHR the renin mRNA level in th e left kidney was significantly suppressed compared with that in the s ham-operated right kidney and with the level in 9-week-old SHR. The re nal renin mRNA level in sham-operated SHR decreased significantly with increasing age, whereas in the Wistar rats the renal renin mRNA level did not change at any age and was not affected by renal denervation. The renal angiotensinogen mRNA level gradually increased with age in b oth rat strains and was not affected by denervation, but much higher l evels were attained in the Wistar rats than in the SHR. Conclusion: Re nal angiotensinogen gene expression was depressed in the SHR, with lit tle evidence of neural regulation at any age in the SHR or the Wistar rats. However, in the SHR the renal sympathetic nerves elevated renal renin gene expression in the prehypertensive stage, but their influenc e decreased as hypertension developed.