Angiotensin-Converting Enzyme Inhibition Linked to Kidney Growth Arrest Specific-6 Protein Expression

Scientists in Singapore have published new data on the effects of angiotensin-converting enzyme inhibitors on mouse kidney growth arrest specific-6 (GAS-6) protein and the AXL subfamily of receptor tyrosine kinases. The study found that chronic dosing with captopril up-regulated GAS-6 and AXL expression in the kidneys of treated mice, with staining predominantly localized to renal tubular cells. These findings suggest that GAS-6 may not be a final common pathway for nitric oxide synthase inhibition-induced renal disease, and could be beneficial in preventing tubular atrophy following persistent systemic hypertension.

Key Takeaways:

• Chronic angiotensin-converting enzyme inhibition up-regulates mouse kidney growth arrest specific-6 (GAS-6) protein and the AXL subfamily of receptor tyrosine kinases.
• GAS-6 and its receptors AXL, MER, and RSE were not present in control and L-NAME-treated mice, but were detectable in mice receiving chronic dosing with captopril, whether treated with captopril only or with captopril and L-NAME.
• Immunohistochemical detection across cases for MER and RSE was rare, whereas AXL-positive staining in the kidney mirrored GAS-6 staining/expression.
• The staining of GAS6 and AXL was predominantly localized to the renal tubular cells.
• Renal tubular GAS-6 expression following captopril treatment was unexpected and could be beneficial in preventing tubular atrophy following the onset of persistent systemic hypertension.

Statistics:

• Four groups of adult male C57BL/6J mice were studied: group 1, untreated controls (tap water for six weeks); group 2, treated orally with a nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 0.325 mg/ml for six weeks); group 3, treated orally with captopril (0.6875 mg/ml for six weeks); group 4, co-treated orally with L-NAME and captopril (same doses for six weeks).
• The study found that GAS-6 and AXL expression was up-regulated in mice receiving chronic dosing with captopril.
• Immunohistochemical detection of MER and RSE was rare, occurring in fewer than 10% of cases.

Sources:

• Eng, P. C., et al. (2008). Chronic angiotensin-converting enzyme inhibition up-regulates mouse kidney growth arrest specific-6 protein and the AXL subfamily of receptor tyrosine kinases. Journal of the Renin-angiotensin-aldosterone System, 9(4), 238-241.
• National University of Singapore, Department of Pharmacology.
• SAGE Publications, USA, 2455 Teller Road, Thousand Oaks, CA 91320, USA.
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