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Original

L-NAME Induces Direct Arteriolar Leukocyte Adhesion, Which Is Mainly Mediated by Angiotensin-II

, , , , , & show all
Pages 443-453 | Received 25 Nov 2004, Accepted 16 Feb 2004, Published online: 10 Jul 2009
 

Abstract

Objective: Acute inhibition (1 h) of nitric oxide synthase (NOS) with L-NAME causes leukocyte recruitment in the rat mesenteric postcapillary venules that is angiotensin-II (Ang-II) dependent. Since 4-h exposure to Ang-II provokes arteriolar leukocyte adhesion, this study was designed to investigate whether subacute (4-h) NOS inhibition also causes this effect.

Methods: Rats were intraperitoneally injected with saline, L-NAME, or 1H-[1,2,4]-oxidazolol-[4,3-a]-quinoxalin-1-one (ODQ). Leukocyte accumulation in the mesenteric microcirculation was examined 4 h later via intravital microscopy. Some groups were pretreated with losartan, an AT1 Ang-II receptor antagonist.

Results: At 4-h, L-NAME caused a significant increase in arteriolar leukocyte adhesion and leukocyte–endothelial cell interactions in postcapillary venules. Mononuclear cells were the predominant leukocytes attached to the arteriolar endothelium. Administration of losartan inhibited L-NAME-induced arteriolar leukocyte adhesion by 90%. L-NAME provoked increased expression of P-selectin, E-selectin, ICAM-1, and VCAM-1 in arterial endothelium, which was attenuated by losartan pretreatment. Inhibition of guanylyl cyclase with ODQ mimicked the effects exerted by L-NAME and losartan also reduced these effects.

Conclusions: NOS inhibition for 4-h results in the attachment of leukocytes to the arterial endothelium, a critical event in disease states such as hypertension and atherosclerosis, which could be prevented by the administration of AT1Ang-II receptor antagonists.

Microcirculation (2005) 12, 443-453. doi:10.1080/10739680590960962

The present study was supported by grant SAF 2002-01482 from Spanish Ministry of Education and Science, Research Groups grant 03/166 from Generalitat Valenciana, and grant MT-7684 from the Canadian Institutes of Health Research (ACI).

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