The role of nitric oxide as an endogenous regulator of platelet and neutrophil activation within the pulmonary circulation of the rabbit.
1. Intravenous (i.v.) administration of adenosine diphosphate (ADP), platelet activating factor (PAF) and thrombin induced a dose-related accumulation of 111indium-labelled platelets within the thoracic region of anaesthetized rabbits. 2. I.v. administration of the inhibitor of NO biosynthesis, L-NG-nitro arginine methyl ester (L-NAME; 10 mg kg-1) significantly potentiated the peak platelet accumulation induced by ADP, PAF and thrombin. Additionally L-NAME prolonged the disaggregation of platelets in comparison to D-NAME (10 mg kg-1). Such changes were reversible by the administration of L-arginine (900 mg kg-1). 3. I.v. administration of PAF induced a small accumulation of 111indium-labelled neutrophils within the pulmonary circulation which could be greatly potentiated by pretreatment of the animals with L-NAME. In contrast, thrombin administration did not cause significant accumulation of 11indium-labelled erythrocytes in the pulmonary circulation of anaesthetized rabbits. 4. Intracarotid (i.c.) administration of thrombin induced a marked accumulation of radiolabelled platelets within the cranial vasculature which was not potentiated by the prior administration of L-NAME (at either 10 mg kg-1 or 100 mg kg-1). 5. These results suggest that endogenous NO may regulate platelet and polymorphonuclear leukocyte activation within the pulmonary but not the cerebral circulation of rabbits.
May
G R
GR
Department of Pharmacology, King's College, University of London.
Crook
P
P
Moore
P K
PK
Page
C P
CP
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002560:Cerebrovascular Circulation; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009504:Neutrophils / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D015539:Platelet Activation; D011652:Pulmonary Circulation; D011817:Rabbits
D010972:Platelet Activating Factor; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester