Angiotensin-II-dependent NHE1 activation in human monocytes

Angiotensin II a potent vasoconstrictor. ha,; been demonstrated to be involved in the pathogenesis, of atherosclerosis. and its complications. Na+/H+ exchanger isoform 1 (NHE1) is related to hypertension activation and can be augmented atherosclerosis-related functions in human monocytes. The purpose of this study IS to investigate in monocytes the signal transduction pathway induced by angiotensin II. In which the Na+/H+ exchanger (NHE1) takes part Monocytes were isolated. and intracellular pH (pHi) was measured by the use of Bis-(carboxyethyl)-5(6)-carboxy-fluorescein acetoxymethylester Super-oxide anions were measured by nitroblue tetrazolium Monocyte binding to laminin-1 was quantified using the myeloperoxidase assay Angiotensin II caused a significant increase in pHi of monocytes. which indicates NHE activation Cariporide.,an NHE1 inhibitor, GF109203X, and Go6976, Inhibitors of isoforms of protein kinase C (PKC). diphenyleneiodonium chloride. the Inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and N-omega-Nitro-L-arginine methyl ester hydrochloride. the inhibitor of nitric oxide (NO) synthase. reversed this effect. Moreover, it was shown that angiotensin II caused an increase in superoxide ion (O-2(-)) levels as well as all increase in monocytes' adhesion to laminin, In relation to controls.. The Use of cariporide inhibited these effects. Furthermore, angiotensin II caused an increase in pHi which was reversed by cariporide in monocytes derived from hypertensive patients Consequently, in monocytes angiotensin II caused NHE1 activation through pathways Involving isoforms of PKC with the participation of O-2(-) and NO In addition, a link between angiotensin II and the atherogenic properties, of monocytes was Shown, where NHE1 plays a central role (c) 2008 American Society of Hypertension. All rights reserved