The role of nitric oxide as an endogenous regulator of platelet and neutrophil activation within the pulmonary circulation of the rabbit

Abstract

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. 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). 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. 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). These results suggest that endogenous NO may regulate platelet and polymorphonuclear leukocyte activation within the pulmonary but not the cerebral circulation of rabbits.

Downregulation of human platelet reactivity by neutrophils. Participation of lipoxygenase derivatives and adhesive proteins.

“…The complexities involved in studying effects of neutrophils on platelets are emphasized by recent contradictory reports in the literature. These range from neutrophil promotion of platelet reactivity (2)(3)(4)(5) to neutrophil blockage of platelet responsiveness (6)(7)(8)(9)(10)(11)(12). The reasons for these differences are not completely understood, but must in part be attributable to methodology.…”

Nitric oxide as a regulator of inflammatory processes

“…NO can also down-regulate neutrophil aggregation and secretion (May et al 1991), and may protect the neutrophil from damage induced by the potent reactive oxygen metabolites that it is capable of producing (Rubanyi et al 1991).…”

Inhibition and stimulation of nitric oxide synthesis in the human forearm arterial bed of patients with insulin-dependent diabetes.

“…In both instances NO synthesis is inhibited by certain analogues of L-arginine, including N0-monomethyl-Larginine (L-NMMA) (21 ), which acts as a competitive, stereospecific inhibitor of NO synthase (22). Systemic inhibition of NO synthesis in animals leads to vasoconstriction (23), a rise in blood pressure (24)(25)(26), and, in some vascular beds under experimental conditions, enhanced platelet adhesion and aggregation (27). In the human forearm, local infusion of L-NMMA causes a near doubling of arteriolar resistance (20), suggesting that basal NO release is an important determinant of resting blood flow.…”