Inappropriately high circulating and intrarenal angiotensin II levels during dietary salt loading exacerbate hypertension in Cyp1a1-Ren-2 transgenic rats.
OBJECTIVE
We evaluated the effects of salt restriction and of increasing dietary salt loading on blood pressure and the renin-angiotensin system in transgenic rats with inducible hypertension.


METHODS
Hypertension was induced in Cyp1a1-Ren-2 rats through dietary administration of the natural xenobiotic indole-3-carbinol (0.3%), which activates the renin gene. Rats were fed either a normal-salt diet (0.6% NaCl), three different high-salt diets (2, 4 and 8% NaCl) or a low-salt diet (<0.04% NaCl). Blood pressure was monitored by radiotelemetry. Angiotensin II (ANG II) levels were determined by radioimmunoassay.


RESULTS
Induction of the renin gene by administration of indole-3-carbinol resulted in normal-salt diet fed animals in the development of severe hypertension that was accompanied by marked increases in plasma and kidney ANG II levels. Feeding the low-salt diet substantially attenuated the development of hypertension. Treatment with the 2 and 4% high-salt diet did not worsen the course of hypertension and did not alter ANG II levels when compared with rats on the normal salt diet. Feeding the 8% high-salt diet exacerbated the course of hypertension and was associated with further strong increases in plasma and kidney ANG II levels.


CONCLUSIONS
Our results demonstrate that after induction of the renin gene in Cyp1a1-Ren-2 transgenic rats inappropriate increases in plasma and kidney ANG II levels in response to very high dietary salt intake are responsible for the development of severe hypertension in this model of inducible renin transgenic rats.
Husková
Zuzana
Z
Department for Experimental Medicine, Institute for Clinical and Experimental Medicine, 1958/9 Vídenská, Prague, Czech Republic.
Vanourková
Zdenka
Z
Erbanová
Michaela
M
Thumová
Monika
M
Opocenský
Martin
M
Mullins
John J
JJ
Kramer
Herbert J
HJ
Bürgelová
Marcela
M
Cervenka
Ludek
L
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D003404:Creatinine / Q000652:urine; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D055647:Rats, Transgenic; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*
C535029:Ren2 protein, rat; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; D000450:Aldosterone; D003404:Creatinine; D019363:Cytochrome P-450 CYP1A1; D012083:Renin