Introduction. Growth arrest specific-6 (GAS-6), a vitamin K-dependent protein, is a potential mediator in progressive and chronic renal disease, specifically as a mediator of abnormal mesangial cell proliferation. Nitric oxide and angiotensin II affect mesangial cell proliferation. However, an association between nitric oxide synthase or angiotensin II on GAS-6 expression in the kidney has not previously been examined. Thus, our aim was to examine the effects of antihypertensive angiotensin-converting enzyme inhibitors and chronic nitric oxide synthase inhibition on the kidney expression of GAS-6 and its receptors AXL, MER and RSE. Methods. 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).At the end of the study, kidneys were placed in fixative and processed to paraffin for immunohistochemical staining. Results. GAS-6 and its receptors were not present in control and L-NAME-treated mice. Positive GAS-6 staining was detectable only in those mice receiving some form of chronic dosing with captopril, whether they were 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 localised to the renal tubular cells. Conclusions. These findings suggest that GAS-6 may not be a final common pathway for nitric oxide synthase inhibition-induced renal disease. 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.
|Number of pages||4|
|Journal||JRAAS - Journal of the Renin-Angiotensin-Aldosterone System|
|Publication status||Published - 1 Dec 2008|
- Growth arrest specific-6
- N-nitro-L-arginine methyl ester
- Nitric oxide synthase