NADPH Oxidase 1 Mediates Acute Blood Pressure Response to Angiotensin II by Contributing to Calcium Influx in Vascular Smooth Muscle Cells

Reactive oxygen species (ROS) and calcium ions (Ca ) are among the major effectors of Ang II (angiotensin II) in vascular smooth muscle cells. ROS are related to Ca signaling or contraction induced by Ang II, but little is known about their detailed functions. Here, NOX (NADPH oxidase), a major ROS...

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Veröffentlicht in:Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2022-05, Vol.42 (5), p.e117-e130
Hauptverfasser: Park, Jung-Min, Do, Van Quan, Seo, Yoon-Seok, Kim, Hyun Jong, Nam, Joo Hyun, Yin, Ming Zhe, Kim, Hae Jin, Kim, Sung Joon, Griendling, Kathy K., Lee, Moo-Yeol
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Sprache:eng
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Zusammenfassung:Reactive oxygen species (ROS) and calcium ions (Ca ) are among the major effectors of Ang II (angiotensin II) in vascular smooth muscle cells. ROS are related to Ca signaling or contraction induced by Ang II, but little is known about their detailed functions. Here, NOX (NADPH oxidase), a major ROS source responsive to Ang II, was investigated regarding its contribution to Ca signaling. Vascular smooth muscle cells were primary cultured from rat aorta. Ca and ROS were monitored mainly using fura-2 and HyPer family probes' respectively. Signals activating NOX were examined with relevant pharmacological inhibitors and genetic manipulation techniques. Ang II-induced ROS generation was found to be biphasic: the first phase of ROS production, which was mainly mediated by NOX1, was small and transient, preceding a rise in Ca , and the second phase of ROS generation, mediated by NOX1 and NOX4, was slow but sizeable, continuing over tens of minutes. NOX1-derived superoxide in the first phase is required for Ca influx through nonselective cation channels. AT1R (Ang II type 1 receptor)-G -PI3K (phosphoinositide 3-kinase γ) signaling pathway was responsible for the rapid activation of NOX1 in the first phase, while in the second phase, NOX1 was further activated by a separate AT1R-Gα -PLC (phospholipase C)-PKC (protein kinase C β) signaling axis. Consistent with these observations, aortas from NOX1-knockout mice exhibited reduced contractility in response to Ang II, and thus the acute pressor response to Ang II was also attenuated in NOX1-knockout mice. NOX1 mediates Ca signal generation and thereby contributes to vascular contraction and blood pressure elevation by Ang II.
ISSN:1079-5642
1524-4636
DOI:10.1161/ATVBAHA.121.317239