-
Views
-
Cite
Cite
Inbal Hazan-Hallevy, Talya Wolak, Ira Lubarsky, Rachel Levy, Esther Paran, P-351: Angiotensin II stimulates NADPH-oxidase and phospholipase A2 activities in phagocytic cells. A possible role of PYK2 and MAP-kinases, ERK and P38, in angiotensin II-signaling, American Journal of Hypertension, Volume 14, Issue S1, April 2001, Page 148A, https://doi.org/10.1016/S0895-7061(01)01948-3
Close - Share Icon Share
Abstract
It has been suggested that the binding of angiotensin II to AT1 receptors activates a cascade of events that leads to stimulation of oxidative stress, the products of which possess remarkable vasoconstrictive qualities. The major enzyme-producing oxidative radical is the enzymatic complex NADPH-oxidase. The effect of angiotensin II on activation of NADPH-oxidase in monocyte and granulocyte from normotensive volunteers and the signaling pathways leading to its activity were investigated. Angiotensin II stimulated a dose-dependent activation of NADPH oxidase in both peripheral blood monocytes and granulocytes, with higher activity obtained in monocytes. Similarly, a dose-dependent activation of NADPH oxidase was demonstrated in the myeloid cell-line PLB-985 differentiated towards neutrophil or monocyte lineages, with higher efficiency observed in the monocytic-like cells. The selective AT1 receptor antagonist, losartan, inhibited NADPH-oxidase activity stimulated by angiotensin II. A high correlation between phospholipase A2 and NADPH-oxidase activities were obtained in angiotensin II-stimulated monocytes, neutrophils or differentiated PLB-985 cells. These results are in accordance with our previous studies demonstrating the essential requirement of cytosolic phospholipase A2 for activation of NADPH-oxidase. Potential upstream components of phospholipase A2 activation were investigated. Angiotensin II stimulated a dose and time-dependent activation of the cytosolic tyrosine kinase, Pyk2, and the MAP-kinases, ERK 1/2 and p38, in differentiated PLB-985 cells. Our results demonstrate the ability of angiotensin II to stimulate phagocytic cells and suggest a possible role of these cells in the pathology of hypertensive disease via the formation of inflammatory mediators.
- angiotensins
- oxidative stress
- losartan
- hypertension
- signal transduction
- angiotensin ii
- cell lines
- cytosol
- granulocytes
- inflammation mediators
- monocytes
- nadph oxidases
- neutrophils
- phospholipase
- phosphotransferases
- protein tyrosine kinase
- enzymes
- pathology
- signal pathway
- signal transduction pathways
- angiotensin ii type 1 receptor blockers
- heart sound a2
