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Adenosine inhibits leukocyte-induced vasoconstriction
T Minamino1, M Kitakaze, K Node
1First Department of Medicine, Osaka University School of Medicine, Japan.
Abstract:
Polymorphonuclear leukocytes (PMNs) can induce endothelium-dependent constriction of vascular rings. Because adenosine inhibits the function of PMNs, we examined the effects of adenosine on the PMN-induced coronary vasoconstriction. We measured changes in the isometric tension of isolated rings of canine coronary arteries suspended in an organ chamber filled with Krebs-Henseleit solution after the addition of autologous PMNs. N-formyl-L-methionyl-leucyl-phenylalanine (FMLP)-stimulated PMNs increased the tension of the coronary artery with the endothelium in a concentration-dependent manner. Treatment of FMLP-stimulated PMNs with adenosine inhibited both the adhesion of PMNs to the endothelium and the PMN-induced vasoconstriction. Stimulation of PMNs with CGS-21680C, but not with cyclohexyladenosine, inhibited both the adhesion of PMNs to the endothelium and the PMN-induced vasoconstriction. However, treatment of coronary arteries with adenosine had no effect on the adherence of PMNs to the endothelium and the PMN-induced constriction. These results suggest that stimulation of adenosine A2a receptors on PMNs may inhibit the PMN-induced vasoconstriction by inhibiting the adhesion of PMNs to the endothelium.
Insights
Adenosine inhibits polymorphonuclear leukocyte (PMN)-induced coronary vasoconstriction by preventing PMN adhesion to the endothelium. This effect is mediated through adenosine A2a receptors on PMNs, not on the coronary arteries themselves.
Area of Science:
- Cardiovascular Physiology
- Immunology
- Pharmacology
Background:
- Polymorphonuclear leukocytes (PMNs) contribute to endothelium-dependent vascular constriction.
- Adenosine is known to modulate immune cell function.
Purpose of the Study:
- To investigate the effect of adenosine on PMN-induced coronary vasoconstriction.
- To determine if adenosine acts directly on PMNs or coronary arteries.
Main Methods:
- Isometric tension measurements of isolated canine coronary artery rings.
- Stimulation of PMNs with N-formyl-L-methionyl-leucyl-phenylalanine (FMLP) and adenosine.
- Assessment of PMN adhesion to the endothelium.
Main Results:
- FMLP-stimulated PMNs caused concentration-dependent coronary vasoconstriction.
- Adenosine treatment of PMNs inhibited both PMN adhesion and vasoconstriction.
- Adenosine A2a receptor agonists (CGS-21680C) mimicked adenosine's inhibitory effects.
- Adenosine had no direct effect on coronary artery tension or PMN adhesion.
Conclusions:
- Adenosine inhibits PMN-induced coronary vasoconstriction.
- The inhibitory effect of adenosine is mediated via adenosine A2a receptors on PMNs.
- Adenosine's action involves reducing PMN adhesion to the endothelium.