NAD(P)H-dependent superoxide production in platelets: The role of angiotensin II and protein kinase C

NAD(P)H-dependent superoxide production in platelets: The role of angiotensin II and protein kinase C Pages 607-613 Richard D. Plumb, Naglaa A. El-Sherbeeny, Lana J. Dixon, Sinead M.T. Hughes, Adrian B. Devine, William J. Leahey, Gary E. McVeigh Preview Purchase PDF (333 K) | Related Articles Abstract | Figures/Tables | References Abstract Objectives: Vascular NAD(P)H oxidase represents a major source for excessive superoxide production in hypertension. Angiotensin II (AngII) can activate NAD(P)H oxidase via the angiotensin II type 1 (AT1) receptor and protein kinase C (PKC). Platelets possess AT1 receptors and all the components of the NAD(P)H oxidase system. We employed this tissue model to explore mechanisms involved in AngII-mediated superoxide production. Design and methods: Platelet suspensions from hypertensive patientsʹ blood were activated with AngII or phorbol 12-myristate 13-acetate (PMA). Inhibitors of NAD(P)H oxidase, PKC, and the AT1 receptor were employed to study their effects on superoxide production. Results: Superoxide production was stimulated by AngII and PMA and attenuated by AT1 receptor antagonists (mean percentage reduction 80.2%, P < 0.01) and inhibitors of PKC (mean reduction 94.8%, P < 0.001) and NAD(P)H oxidase (mean reduction 100%, P < 0.001). Conclusions: AngII stimulates platelet superoxide production through activation of vascular NAD(P)H oxidase via the AT1 receptor and PKC.