NITRIC-OXIDE SYNTHASE AND RENIN-ANGIOTENSIN SYSTEM GENE-EXPRESSION INSALT-SENSITIVE AND SALT-RESISTANT SABRA RATS

The molecular mechanisms of salt sensitivity and the contribution of t he kidney to salt-induced hypertension in Sabra rats are imperfectly d efined. We investigated the expression of the nitric oxide (NO) system (endothelial, inducible, and neural NO synthases) and renin-angiotens in 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 deoxycorticoste rone acetate (DOCA)-salt treatment. We also looked for immunocytochemi cal evidence of angiotensin II, the effector peptide of the renin-angi otensin system. Inducible and neural NO synthase gene expression value s were lower in SBH/y than in SBN/y before and after DOCA-salt treatme nt. The gene expression level of endothelial NO synthase was not diffe rent 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 kidney s of SBH/y rats, whereas angiotensinogen gene expression was significa ntly lower in SBN/y. After DOCA-salt treatment, renin gene expression was strongly suppressed in both strains but more so in SBH/y. Angioten sinogen gene expression, on the other hand, was increased by DOCA salt in SBN/y rats so that the two strains were no longer different. Angio tensin II immunoreactivity was significantly higher in SRN/y than in S BN/y; however, after DOCA salt, immunoreactivity in both strains was n o longer detectable. Angiotensin II type 1A receptor gene expression w as 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 syn thase gene expression in SBH/y and SBN/y. Inducible and neural NO synt hase gene expression values were less in SBH/y than in SBN/y, independ ent of DOCA-salt administration. Thus, the NO system could explain, at least in part, the salt resistance of SBN/y.