EFFECT OF GENETIC DEFICIENCY OF ANGIOTENSINOGEN ON THE RENIN-ANGIOTENSIN SYSTEM

This study examined expression of renin-angiotensin system (RAS) compo nent mRNAs in angiotensinogen gene knockout (Atg-/-) mice. Wild-type ( Atg+/+) and Atg-/- mice were fed a normal-salt (0.3% NaCl) or high-sal t (4% NaCl) diet for 2 weeks. Angiotensinogen, renin, angiotensin-conv erting enzyme (ACE), angiotensin II type la receptor (AT(1A)), and ang iotensin II type 2 receptor (AT(2)) mRNA levels were measured by North ern blot analysis. In Atg+/+ mice, activities of circulating RAS and r enal angiotensinogen mRNA level were decreased by salt loading, wherea s levels of renal and cardiac ACE; renal, brain, and cardiac AT(1A); a nd brain and cardiac AT(2) mRNA were increased by salt loading. Althou gh activities of circulating RAS were not detected in Atg-/- mice, sal t loading increased blood pressure in Atg-/- mice. In Atg-/- mice, ren al renin mRNA level was decreased by salt loading; in contrast, salt l oading increased renal AT(1A) and cardiac AT(2) mRNA levels in Ag-/- m ice, and these activated levels in Atg-/- mice were higher than those in Atg+/+ mice fed the high-salt diet. Thus, expression of each compon ent of the RAS is regulated in a tissue-specific manner that is distin ct from other components of systemic and local RAS and that appears to be mediated by a mechanism other than changes in the circulating or t issue levels of angiotensin peptides.