The Effects of Angiotensin II, Olmesartan and PD123,319 on Protein Kinase C in STZ Induced Rat Vascular Smooth Muscle Cell Culture

Abstract

Protein kinase C (PKC) is a promoter enzyme that plays a vital role in signal transduction of vascular smooth muscle cells (VSMCs). It has numerous vascular functions, such as vascular cell growth, cytokine activation and angiogenesis. But, these mechanisms are deteriorating in diabetes mellitus. Angiotensin II (Ang II) effects on vascular structure binding Ang II type-1 and type-2 receptors (ATR1 and ATR2) and stimulates PKC mostly through ATR1s. We aim to investigate the effects of Ang II, Olmesartan and PD123,319 on PKC levels of healthy and streptozotocin (STZ) induced rat VSMCs (H-VSMCs and STZ-VSMCs) in this study. The primary culture of VSMCs were isolated from thoracic aorta of healthy and STZ (45 mg/kg, given via the tail vein) induced Wistar rats. PKC levels were measured in H-VSMCs and STZ-VSMCs by enzyme-linked immunosorbent assay (ELISA). In H-VSMCs, Ang II group compared to the control group, PKC levels decreased significantly (P = 0.000); whereas, Ang II group compared to control, PKC levels were higher, but not significantly in STZ-VSMCs (P = 0.088). PKC levels were increased in Ang II+Olmesartan (P = 0.000) and Ang II+PD123,319 (P = 0.000) groups compared to Ang II group in H-VSMCs, but in STZ-VSMCs, PKC levels in Ang II+Olmesartan (P = 0.001) and Ang II+PD123,319 (P = 0.000) groups compared to Ang II group were decreased significantly. Ang II, its receptors and PKC seem to modulate each other and may have a relationship in hyperglycemic conditions. Also, considering that, ATR1 blocker (ATR1B) Olmesartan and ATR2 blocker (ATR2B) PD123,319 may be protective against vascular injury by reducing PKC levels in STZ-VSMCs.