Nitric oxide synthase inhibitor augments post-ischemic leukocyte adhesion in the cerebral microcirculation in vivo

The objective was to examine the effect of the nitric oxide synthase inhibi tor N-omega-nitro-L-arginine methyl ester (L-NAME) on leukocyte adhesion in the cerebral microcirculation during reperfusion following partial forebra in ischemia in the rat Intravital fluorescence video-microscopy through a c losed cranial window was used to visualize leukocyte-endothelium interactio n in small pial veins of 15-100 mu m diameter. Forebrain ischemia was produ ced by the ligation of both common carotid arteries plus elevation of the i ntracranial pressure to 20 mmHg far 60 min. The number of leukocytes adheri ng to the endothelium for longer than 3 sec was determined during ischemia (5 min and 60 min) and during reperfusion (5 min and 60 min). Two experimen tal groups were treated with either L-NAME or its inactive enantiomer D-NAM E (20 mg kg(-1) i.v.) 30 min prior to reperfusion. In a third group, also t reated with D-NAME, post-ischemic hyperemia was prevented by lowering the I CP without removing the occlusion of common carotid arteries (partial reper fusion). The velocity of flow adjacent to the endothelial surface of pial v eins was measured by tracking the movement of fluorescently labeled red blo od cells as flow markers before and after ischemia. During ischemia, the nu mber of adhering leukocytes increased approximately two-fold at 5 min, and threefold at 60 min. In the D-NAME-treated group with complete reperfusion, leukocyte adhesion returned to the baseline level by 60 min of reperfusion . However, in the L-NAME-treated group, leukocyte adhesion remained elevate d at 60 min of reperfusion. Post-ischemic flow velocity was significantly d ecreased (-66%) from control after L-NAME treatment whereas it was increase d (+ 53%) in the D-NAME-treated group. In the partial reperfusion group, le ukocyte adhesion continued to increase after the first hour of ischemia and reached a level 2.7-fold over baseline at 60 min reperfusion. Flow velocit y remained below control (-26%) at 60 min reperfusion. Leukocyte adhesion w as absent in pial arteries and no plugging by leukocytes was observed in co rtical capillaries. The results suggest that leukocyte adhesion in small pi al veins increases during 1 h forebrain ischemia and continues to increase during reperfusion if the velocity of flow or shear rate is low. The increa se in leukocyte adhesion is reversible if flow velocity is elevated during reperfusion. L-NAME prevents post-ischemic hyperemia and augments leukocyte adhesion principally via a decrease in velocity or shear rate.