|dc.description.abstract||With the relationship between endothelin-1 (ET-1) stimulation and reactive
oxygen species (ROS) production unknown in adventitial fibroblasts, I examined the
ROS response to ET-1 and angiotensin (Ang II).
ET-1 -induced ROS peaked following 4 hrs of ET-1 stimulation and was
inhibited by an ETA receptor antagonist (BQ 123, 1 uM) an extracellular signal-regulated
kinase (ERK) 1/2 inhibitor (PD98059, 10 uM), and by both a specific, apocynin (10 uM),
and non-specific, diphenyleneiodonium (10 uM), NAD(P)H oxidase inhibitor. NOX2
knockout fibroblasts did not produce an ET-1 induced change in ROS levels.
Ang II treatment increased ROS levels in a biphasic manner, with the second peak
occurring 6 hrs following stimulation. The secondary phase of Ang II induced ROS was
inhibited by an ATi receptor antagonist, Losartan (100 uM) and BQ 123.
In conclusion, ET-1 induces ROS production primarily through an ETA-ERKl/2
NOX2 pathway, additionally, Ang II-induced ROS production also involves an ETa