Guanylyl cyclase/natriuretic peptide receptor-A gene disruption causes increased adrenal angiotensin II and aldosterone levels.

Abstract

Disruption of the guanylyl cyclase-A/natriuretic peptide receptor-A (GC-A/NPRA) gene leads to elevated arterial blood pressure and congestive heart failure in mice lacking NPRA. This study was aimed at determining whether Npr1 (coding for GC-A/NPRA) gene copy number affects adrenal ANG II and aldosterone (Aldo) levels in a gene-dose-dependent manner in Npr1 gene-targeted mice. Adrenal ANG II and Aldo levels increased in 1-copy mice compared with 2-copy mice, but decreased in 3-copy and 4-copy mice. In contrast, renal ANG II levels decreased in 1-copy (25%), 3-copy (38%), and 4-copy (39%) mice compared with 2-copy mice. The low-salt diet stimulated adrenal ANG II and Aldo levels in 1-copy (20 and 2,441%), 2-copy (15 and 2,339%), 3-copy (20 and 424%), and 4-copy (31 and 486%) mice, respectively. The high-salt diet suppressed adrenal ANG II and Aldo levels in 1-copy (46 and 29%) and 2-copy (38 and 17%) mice. On the other hand, the low-salt diet stimulated renal ANG II levels in 1-copy (45%), 2-copy (45%), 3-copy (59%), and 4-copy (48%) mice. However, the high-salt diet suppressed renal ANG II levels in 1-copy (28%) and 2-copy (27%) mice. In conclusion, NPRA signaling antagonizes adrenal ANG II and Aldo levels in a gene-dose dependent manner. Increased adrenal ANG II and Aldo levels may play an important role in elevated arterial blood pressure and progressive hypertension, leading to renal and vascular injury in Npr1 gene-disrupted mice.

• Authors: Di Zhao, Elangovan Vellaichamy, Naveen K Somanna, Kailash N Pandey
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 293 Issue 1 Pg. F121-7 (Jul 2007) ISSN: 1931-857X [Print] United States
• PMID: 17389676 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Sodium, Dietary
• Angiotensin II
• Aldosterone
• Guanylate Cyclase
• Receptors, Atrial Natriuretic Factor
• atrial natriuretic factor receptor A

Topics

• Adrenal Glands (metabolism)
• Aldosterone (metabolism)
• Angiotensin II (metabolism)
• Animals
• Blood Pressure (physiology)
• Diet
• Gene Dosage
• Gene Duplication
• Guanylate Cyclase (genetics, physiology)
• Kidney (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptors, Atrial Natriuretic Factor (genetics, physiology)
• Sodium, Dietary (pharmacology)