Rapid fusion of granules with neutrophil cell membranes in hypertensive patients may increase vascular damage

In essential hypertension (EHT) the presence of a metabolic syndrome increa ses the risk of cardiovascular disease. A cell membrane abnormality is impl icated but its role in cardiovascular disease is unclear. Neutrophil accumu lation, which occurs by beta (2)-integrin (CD11b/CD18) expression, followed by release of proinflammatory factors from primary vesicles is an importan t factor in vascular damage. CD11b and CD69 expression on neutrophils from normal controls and EHT patie nts was determined by fluorescence-activated cell scanning. Neutrophils wer e activated with phorbol myristate acetate (PMA). Protein kinase C (PKC) an d calpain were inhibited with bisindolylmaleimide and E64d, respectively. In EHT patients CD11b was not increased on neutrophils at rest. However, EH T neutrophils more readily expressed CD11b on incubation in phosphate-buffe red saline and more cells went on to exocytose primary granules indicated b y expression of CD69. Stimulation with PMA caused more rapid activation in EHT neutrophils with expression of CD11b, followed rapidly by exocytosis of primary granules. Bisindolylmaleimide slowed but did not prevent CD11b exp ression, which, together with primary granule exocytosis, continued to be f aster in EHT neutrophils. E64d also slowed but did not prevent either CD11b expression or primary granule exocytosis, but this inhibitor did abolish t he difference between NC and EHT neutrophils. The membrane abnormality in EHT may contribute to cardiovascular risk by in creasing the rate of vesicle fusion with the cell membrane to increase neut rophil accumulation and release of inflammatory agents at sites of vascular damage. Calpain activation may be the rate-limiting component that is abno rmal. Am J Hypertens 2001;14:927-933 (C) 2001 American Journal of Hypertens ion, Ltd.