Interaction of human platelets and leukocytes in modulation of vascular tone.
We tested the hypothesis that the vasodilator response to human platelets is modulated by polymorphonuclear leukocytes (PMNs). Responses to platelets activated with thrombin, as well as PMNs activated with N-formylmethionyl-leucyl-phenylalanine (FMLP), were examined in perfused rabbit carotid arteries in vitro. Activation of platelets produced marked dilatation, and activation of PMNs produced modest constriction in arteries preconstricted with phenylephrine. Vasodilator responses to platelets were greatly impaired during infusion of activated PMNs. Pretreatment of PMNs with superoxide dismutase (SOD) partially restored dilator responses to platelets. Because SOD only partially restored vasodilator responses to platelets, we tested the possibility that adenosine-diphosphatase (ADPase) activity of PMNs may degrade ADP released by platelets and thus reduce vasodilator responses. After incubation with PMNs, dilator responses to ADP, but not acetylcholine, were significantly impaired. These findings indicate that vasodilatation produced by activated human platelets is profoundly impaired by activated leukocytes. We conclude that two mechanisms may account for this effect: 1) endothelium-derived relaxing factor, released in response to platelet-derived ADP, is inactivated by superoxide anion generated by activated PMNs and 2) ADP is degraded by ADPase activity of PMNs. We speculate that platelet-leukocyte interaction may have important effects on vasomotor tone.
Kaul
S
S
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Waack
B J
BJ
Padgett
R C
RC
Brooks
R M
RM
Heistad
D D
DD
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D017536:Carotid Artery, Common / Q000187:drug effects / Q000502:physiology*; D004873:Ergolines / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D015539:Platelet Activation; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D012702:Serotonin Antagonists / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D004873:Ergolines; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011450:Prostaglandin Endoperoxides, Synthetic; D017482:Receptors, Thromboxane; D012702:Serotonin Antagonists; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D019335:Nitroarginine; D013928:Thromboxane A2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D001120:Arginine; D013482:Superoxide Dismutase; C032663:LY 53857; D000109:Acetylcholine