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

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 I (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 patients' 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 AT I 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 AT I receptor and PKC. (C) 2005 The Canadian Society of Clinical Chemists. All rights reserved.