AMINOGUANIDINE-PROVOKED LEUKOCYTE ADHERENCE TO RAT MESENTERIC VENULES - ROLE OF CONSTITUTIVE NITRIC-OXIDE SYNTHASE INHIBITION

1 The effects of aminoguanidine on neutrophil adherence to venules and on the diameter of arterioles in the mesenteric vascular bed of the pentobarbitone-anaesthetized rat have been compared with those of the nitric oxide synthase inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME). 2 Administration of L-NAME (1-10 mg kg(-1) i.v.) caused a dose-dependent increase in leukocyte adherence and a reduction in leukocyte rolling velocity in postcapillary venules of the rat mesentery over 1 h. 3 Likewise, aminoguanidine (10-100 mg kg(-1) i.v.) dose-dependently increased leukocyte adherence and decreased leukocyte rolling velocity over 1 h. 4 Both L-NAME and aminoguanidine caused a dose-dependent reduction in mesenteric arteriolar diameter and an increase in systemic arterial blood pressure. 5 The effects of aminoguanidine (50 mg kg(-1), i.v.) on leukocyte adherence, arteriolar diameter and on blood pressure were significantly reversed by pretreatment with L-arginine (300 mg kg(-1), i.v.). 6 These findings indicate that, like L-NAME, aminoguanidine can acutely promote leukocyte adherence to the mesenteric venular wall and reduce arteriolar diameter. Moreover, these acute effects were reversed by L-arginine, suggesting they are mediated through inhibition of constitutive NO synthase.