PMID:10076178

Citation	Tamura, K, Yokoyama, N, Sumida, Y, Fujita, T, Chiba, E, Tamura, N, Kobayashi, S, Kihara, M, Murakami, K, Horiuchi, M and Umemura, S (1999) Tissue-specific changes of type 1 angiotensin II receptor and angiotensin-converting enzyme mRNA in angiotensinogen gene-knockout mice. J. Endocrinol. 160:401-8
Abstract	This study examined whether type 1 angiotensin II receptor (AT1) and angiotensin-converting enzyme (ACE) mRNAs are regulated during dietary salt loading in angiotensinogen gene-knockout (Atg-/-) mice which are genetically deficient in endogenous production of angiotensin II. Wild-type (Atg+/+) and Atg-/- mice were fed a normal-salt (0.3% NaCl) or a high-salt (4% NaCl) diet for 2 weeks. The mRNA levels were measured by Northern blot analysis. In Atg+/+ mice, concentrations of plasma angiotensin peptides were decreased by salt loading, whereas the treatment increased the brainstem, cardiac, pulmonary, renal cortex, gastric and intestinal AT1 mRNA levels. Salt loading also enhanced renal cortex ACE mRNA levels in Atg+/+ mice. Although plasma angiotensin peptides and urinary aldosterone excretion were not detected in Atg-/- mice, salt loading increased blood pressure in Atg-/- mice. In Atg-/- mice, pulmonary, renal cortex, gastric and intestinal AT1, and renal cortex and intestinal ACE mRNA levels were higher than those in Atg+/+ mice. However, salt loading upregulated AT1 mRNA expression only in the liver of Atg-/- mice, and the treatment did not affect ACE mRNA levels in Atg-/- mice. Furthermore, although the levels of ACE enzymatic activity showed the same trend with the ACE mRNA levels in the lung, renal cortex and intestine of both Atg-/- and Atg+/+ mice, the results of radioligand binding assay showed that cardiac expression of AT1 protein was regulated differently from AT1 mRNA expression both in Atg-/- and Atg+/+ mice. Thus, expression of AT1 and ACE is regulated by salt loading in a tissue-specific manner that appears to be mediated, at least partly, by a mechanism other than changes in the circulating or tissue levels of angiotensin peptides.
Links	PubMed
Keywords	Angiotensin II/genetics; Angiotensin II/metabolism; Animals; Blotting, Northern; Brain Stem/metabolism; Intestines/metabolism; Kidney Cortex/metabolism; Liver/metabolism; Lung/metabolism; Mice; Mice, Knockout; Myocardium/metabolism; Peptidyl-Dipeptidase A/genetics; RNA, Messenger/metabolism; Receptors, Angiotensin/genetics; Receptors, Angiotensin/metabolism; Sodium Chloride, Dietary/administration & dosage; Stomach/metabolism
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