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, NG-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.
Lopez-Belmonte
J
J
Wellcome Foundation Ltd., Beckenham, Kent.
Whittle
B J
BJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology; D001794:Blood Pressure / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology; D008642:Mesenteric Veins / Q000187:drug effects* / Q000201:enzymology*; D019331:NG-Nitroarginine Methyl Ester; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D014699:Venules / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology
D004791:Enzyme Inhibitors; D006146:Guanidines; D001120:Arginine; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester