Aminoguanidine-provoked leukocyte adherence to rat mesenteric venules: role of constitutive nitric oxide synthase inhibition

Br J Pharmacol. 1995 Nov;116(6):2710-4. doi: 10.1111/j.1476-5381.1995.tb17231.x.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Arterioles / anatomy & histology
  • Arterioles / drug effects
  • Arterioles / enzymology
  • Blood Pressure / drug effects
  • Cell Adhesion / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Guanidines / pharmacology*
  • Male
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / enzymology
  • Mesenteric Veins / drug effects*
  • Mesenteric Veins / enzymology*
  • NG-Nitroarginine Methyl Ester
  • Neutrophils / cytology
  • Neutrophils / drug effects*
  • Neutrophils / physiology
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Rats
  • Rats, Wistar
  • Venules / anatomy & histology
  • Venules / drug effects
  • Venules / enzymology

Substances

  • Enzyme Inhibitors
  • Guanidines
  • Arginine
  • Nitric Oxide Synthase
  • pimagedine
  • NG-Nitroarginine Methyl Ester