Angiotensin II is involved in nitric oxide synthase and cyclo-oxygenase inhibition-induced leukocyte-endothelial cell interactions in vivo

1 Chronic inhibition of nitric oxide synthase (NOS) provokes a hypertensive state which has been shown to be angiotensin II (Ang-II) dependent. In add ition to raising blood pressure, NOS inhibition also causes leukocyte adhes ion. The present study was designed to define the role of Ang-II in hyperte nsion and in the leukocyte-endothelial cell interactions induced by acute N OS or cyclooxygenase (COX) inhibition using intravital microscopy within th e rat mesenteric microcirculation. 2 While pretreatment with an Ang-II ATI receptor antagonist (losartan) reve rsed the prompt increase in mean arterial blood pressure (MABP) caused by i ndomethacin, it had no effect on the increase evoked by systemic L-NAME adm inistration. 3 Pretreatment with losartan inhibited the leukocyte rolling flux, adhesion and emigration which occurs after 60 min NOS inhibition by 83, 80 and 70% respectively, and returned leukocyte rolling velocity to basal levels. 4 Losartan significantly reduced the leukocyte-endothelial cell interaction elicited by COX inhibition. In contrast, leukocyte recruitment induced by acute mast cell activation was not inhibited by losartan. 5 ATI receptor blockade also prevented the drop in haemodynamic parameters such as mean red blood cell velocity (V-mean) and shear rate caused by NOS and COX inhibition. 6 In this study, we have demonstrated a clear role for Ang-II in the leukoc yte-endothelial cell interactions and haemodynamic changes which arise in t he absence of NO or prostacyclin (PGI(2)). This is of interest since leukoc yte recruitment, which culminates in the vascular lesions that occur in hyp ertension, atherosclerosis and myocardial ischemia-reperfusion injury, migh t be prevented using AT(1) Ang-II receptor antagonists.