ABNORMAL REGULATION OF PROXIMAL TUBULE RENIN MESSENGER-RNA IN THE DAHL RAPP SALT-SENSITIVE RAT/

Background. The precise pathogenesis of salt-sensitive hypertension in the Dahl rat is unknown. Abnormalities in renal hemodynamics and NaCl handling have been implicated, and may relate to changes in the activ ity of the intrarenal renin-angiotensin system. Methods. Circulating, juxtaglomerular and intrarenal (glomerular and proximal tubular) renin were studied in Dahl/Rapp salt-sensitive and salt-resistant rats fed with a normal (0.5%) or high (4%) NaCl diet. Circulating and juxtaglom erular renin were assessed by measurement of plasma renin activity and renin secretory rates. Glomerular and proximal tubular renin mRNA wer e assessed by microdissection and quantitative competitive RT-PCR. Res ults. Circulating and juxtaglomerular renin were suppressed by high di etary NaCl in salt-sensitive rats (plasma renin activity, 0.5%, 10.9 /- 0.7 vs. 4%, 7.9 +/- 0.3 ng/ml/hr, P < 0.05; renin secretory rate, 0 .5% 220 +/- 32 vs. 4%, 58 +/- 5 ng/mg/hr, P < 0.05). Glomerular renin mRNA was also suppressed by the higher salt diet in salt-sensitive ani mals (0.5%, 411 +/- 84 vs. 4%, 67 +/-: 22 x 10(3) copies/glomerulus, P < 0.05). In contrast, proximal tubular renin was not suppressed by a high NaCl diet in salt-sensitive animals (0.5%, 13.9 +/- 2.7 vs. 4%, 1 2.1 +/- 3.6 x 10(3) copies/mm tubule, P = NS), but was suppressed in s alt-resistant rats (0.5%, 9.5 +/- 2.8 vs. 4%, 3.2 +/- 1.2 x 10(3) copi es/mm, P < 0.05). Conclusions. Failure to suppress proximal tubular re nin in response to high dietary NaCl may result in increased local gen eration of angiotensin II and enhanced proximal tubular NaCl absorptio n, and thereby contribute to the generation of salt sensitive hyperten sion.