Angiotensin II stimulates proliferation of adventitial fibroblasts cultured from rat aortic explants

It has been proposed that the local renin-angiotensin system is activated i n the adventitia after vascular injury. However, the physiological role of Angiotensin II (Ang II) in the adventitia has not been studied at a cellula r level. This study was designed to assess the role of Ang II in the growth response of cultured adventitial fibroblasts (AFs). Adventitial explants o f the rat thoracic aorta showed outgrowth of AFs within 5-7 days. Ang II ca used hyperplastic response of AF cultures. The Ang Ii-induced mitogenic res ponse of AFs was mediated primarily by the AT(1) receptor, Ang II caused a rapid induction of immediate early genes (c-fos, c-myc and jun B). Inductio n of c-fos expression was fully blocked by an AT(1) receptor antagonist but not by an AT(2) receptor antagonist. Epidermal growth factor (EGF), platel et-derived growth factor-BB (PDGF-BB) and basic fibroblast growth factor (b FGF) induced DNA synthesis in AFs. Go-stimulation of AFs with the growth fa ctors and Ang II potentiated the incorporation of H-3-thymidine into DNA, R esults from this study indicate that Ang II causes mitogenesis of AFs via A T1 receptor stimulation and potentiates the responses to other mitogens, Th ese data suggest that the Ang II may play an important role in regulating A F function during vascular remodeling following arterial injury.