Nitric oxide synthase and renin-angiotensin system gene expression in salt-sensitive and salt-resistant Sabra rats.
The molecular mechanisms of salt sensitivity and the contribution of the kidney to salt-induced hypertension in Sabra rats are imperfectly defined. We investigated the expression of the nitric oxide (NO) system (endothelial, inducible, and neural NO synthases) and renin-angiotensin system (renin, angiotensinogen, and angiotensin II type 1A receptor) gene components in the kidneys of SBN/y (salt-resistant) and SBH/y (salt-sensitive) Sabra rat substrains, with and without deoxycorticosterone acetate (DOCA)-salt treatment. We also looked for immunocytochemical evidence of angiotensin II, the effector peptide of the renin-angiotensin system. Inducible and neural NO synthase gene expression values were lower in SBH/y than in SBN/y before and after DOCA-salt treatment. The gene expression level of endothelial NO synthase was not different in SBH/y and SBN/y, either with or without DOCA salt. Renin gene expression was significantly higher in kidneys of SBN/y than in kidneys of SBH/y rats, whereas angiotensinogen gene expression was significantly lower in SBN/y. After DOCA-salt treatment, renin gene expression was strongly suppressed in both strains but more so in SBH/y. Angiotensinogen gene expression, on the other hand, was increased by DOCA salt in SBN/y rats so that the two strains were no longer different. Angiotensin II immunoreactivity was significantly higher in SBN/y than in SBH/y; however, after DOCA salt, immunoreactivity in both strains was no longer detectable. Angiotensin II type 1A receptor gene expression was not different between the two strains, either before or after DOCA-salt administration. We conclude that DOCA salt induced a decrease in the activity of the renin-angiotensin system but did not change NO synthase gene expression in SBH/y and SBN/y. Inducible and neural NO synthase gene expression values were less in SBH/y than in SBN/y, independent of DOCA-salt administration. Thus, the NO system could explain, at least in part, the salt resistance of SBN/y.
Lippoldt
A
A
Franz Volhard Clinic and the Max Delbrück Center for Molecular Medicine, Humboldt University, Berlin, Germany.
Gross
V
V
Schneider
K
K
Hansson
A
A
Nadaud
S
S
Schneider
W
W
Bader
M
M
Yagil
C
C
Yagil
Y
Y
Luft
F C
FC
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D003900:Desoxycorticosterone / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D004730:Endothelium, Vascular / Q000201:enzymology; D004790:Enzyme Induction; D015870:Gene Expression; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D008297:Male; D009420:Nervous System / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000235:genetics*; D051381:Rats; D011922:Rats, Mutant Strains / Q000235:genetics*; D012016:Reference Values; D012084:Renin-Angiotensin System / Q000235:genetics*; D012965:Sodium Chloride / Q000494:pharmacology*
D000804:Angiotensin II; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D019001:Nitric Oxide Synthase