The Role of Angiotensin II and Endothelin-1 on the Growth of Arterial and Venous Smooth Muscle Cells

Kim, Seung Jung

Abstract

BACKGROUND: Hemodialysis vascular access stenosis is caused by the proliferation of vascular smooth muscle cells (SMC), and the stenotic lesions occur primarily at the graft-vein anastomosis or venous site. Angiotensin II (Ang II) and endothelin- 1 (ET-1) have been implicated in the proliferation of SMC, but the relative responsiveness of arterial and venous SMC to Ang II or ET-1 is unknown.
METHODS
Human aortic and venous SMC were cultured in a ATCC medium containing 10% serum. Ang II (1-1000 nmol/L), ET-1 (0.1-1 micronmol/L), captopril (1-10 micronmol/L), losartan (1-10 micronmol/L), BQ123 (1 micronmol/L) or BQ788 (1 micronmol/L) were added. After 72 hours, we subjected the cell to a mitochondrial enzymatic (methylthiazoletetrazolium, MTT) assay in order to assess the cell proliferation. We used RT- PCR to observe Ang II or ET-1 receptors.
RESULTS
Ang II increased the proliferation of aortic SMC in a dose-dependent manner, and losartan (not captopril) inhibited the effects of Ang II. However, Ang II failed in increasing the proliferation of venous SMC. Contrary to our expectation, it was ET-1 that increased the proliferation of venous SMC, although it failed to increase the proliferation of aortic SMC. Both BQ123 and BQ788 inhibited the effects of ET-1 in venous SMC. Both aortic and venous SMC had receptors for Ang II and ET-1.
CONCLUSION
This study suggests that strategies for the prevention of vascular access stenosis should take into account the fact that lesions at venous sites may respond differently to various anti-proliferative drugs than do those at arterial sites.