Premium
Disruption of natriuretic peptide receptor A gene increases adrenal angiotensin II and aldosterone levels
Author(s) -
Zhao Di,
Somanveen K,
Vellaichamy Elangovan,
Pandey Kailash N
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1251-a
Subject(s) - medicine , endocrinology , angiotensin ii , copy number variation , aldosterone , renin–angiotensin system , receptor , chemistry , biology , gene , blood pressure , genetics , genome
Disruption of natriuretic peptide receptor‐A (NPRA) gene ( Npr1 ) leads to elevated blood pressure in mice. NPRA signaling counteracts the renin‐angiotensin‐aldosterone system (RAAS). We studied whether Npr1 gene copy number affects adrenal angiotensin II (Ang II) and aldosterone (ALDO) levels in Npr1 gene‐targeted mice. Adrenal Ang II and ALDO levels increased in 1‐copy (15%, p<0.05; 38%, p<0.05) mice, but decreased in 3‐copy (17%, p<0.05; 13%, p<0.05) and 4‐copy (33%, p<0.01; 38%, p<0.001) mice as compared with 2‐copy mice. Renal Ang II levels decreased in 1‐copy (25%, p<0.05), 3‐copy (38%, p<0.01) and 4‐copy (39%, p<0.01) mice. Low salt diet stimulated adrenal Ang II and ALDO levels in 1‐copy (20%, p<0.05; 2441%, p<0.001), 2‐copy (15%, p<0.05; 2339%, p<0.001), 3‐copy (20%, p<0.05; 424%, p<0.001) and 4‐copy (31%, p<0.05; 486%, p<0.001) mice. Renal Ang II levels were similarly stimulated in 1‐copy (45%, p<0.05), 2‐copy (45%, p<0.05), 3‐copy (59%, p<0.05) and 4‐copy (48%, p<0.05) mice. High salt diet suppressed adrenal Ang II and ALDO levels in 1‐copy (46%, p<0.001; 29%, p<0.05) and 2‐copy (38%, p<0.01; 17%, p<0.05) mice and suppressed renal Ang II levels in 1‐copy (28%, p<0.05) and 2‐copy (27%, p<0.05) mice. The present findings indicate that increased adrenal Ang II and ALDO levels play an important role in elevated blood pressure in Npr1 gene‐disrupted mice.