Je. Tank et al., ABNORMAL REGULATION OF PROXIMAL TUBULE RENIN MESSENGER-RNA IN THE DAHL RAPP SALT-SENSITIVE RAT/, Kidney international, 54(5), 1998, pp. 1608-1616
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.