Abnormal regulation of proximal tubule renin mRNA 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 activity 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 juxtaglomerular renin were assessed by measurement of plasma renin activity and renin secretory rates. Glomerular and proximal tubular renin mRNA were assessed by microdissection and quantitative competitive RT-PCR.


RESULTS
Circulating and juxtaglomerular renin were suppressed by high dietary 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 animals (0.5%, 411 +/- 84 vs. 4%, 67 +/- 22 x 103 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%, 12.1 +/- 3.6 x 103 copies/mm tubule, P = NS), but was suppressed in salt-resistant rats (0.5%, 9.5 +/- 2.8 vs. 4%, 3.2 +/- 1.2 x 103 copies/mm, P < 0. 05).


CONCLUSIONS
Failure to suppress proximal tubular renin in response to high dietary NaCl may result in increased local generation of angiotensin II and enhanced proximal tubular NaCl absorption, and thereby contribute to the generation of salt sensitive hypertension.
Tank
J E
JE
Department of Internal Medicine, University of Texas Southwestern Medical Center and Dallas VA Medical Center, Dallas, Texas, USA.
Moe
O W
OW
Henrich
W L
WL
D000818:Animals; D005786:Gene Expression Regulation; D006973:Hypertension / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*
D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D012083:Renin