Leukocyte-induced acute endothelial dysfunction in middle cerebral artery in rabbits. Response to aggregating platelets.
OBJECTIVE
Recent evidence suggests a possible role for leukocytes in angiospastic reactions of large cerebral arteries. This study examined the effect of activation of endogenous circulating leukocytes on endothelium-dependent relaxation in the middle cerebral artery in rabbits.


METHODS
Leukocytes were activated by rapid injection of either 40 micrograms/kg phorbol 12-myristate 13-acetate, or 0.2 mg/kg N-formyl-methionyl-leucylphenylalanine into the left carotid artery. Control rabbits received an equal volume of vehicle. Concentration-dependent isometric tension responses of the left and right middle cerebral artery to the dilators acetylcholine, ADP, sodium nitroprusside, or calcium ionophore (A23187), as well as to aggregating platelets, were compared in vitro in control animals and in animals killed 10 minutes after the injection of leukocyte activators in normal and leukocyte-depleted rabbits.


RESULTS
In the control animals there was no significant difference in the reactivity of the left and right middle cerebral arteries. The injection of the leukocyte activators led to enhanced contractile responses to aggregating platelets and a significant reduction in the endothelium-dependent relaxation in response to acetylcholine, ADP, and A23187 in the left middle cerebral artery (the injected side), whereas the effect of an endothelium-independent dilator sodium nitroprusside remained unchanged. In leukocyte-depleted rabbits the injection of either of the leukocyte activators used did not induce significant changes in the reactivity of the left middle cerebral artery.


CONCLUSIONS
Intravascular leukocyte activation appears to induce an acute disturbance of the endothelium-dependent relaxation. Under these conditions, platelet activation might result in marked angiospastic reactions of large cerebral arteries.
Laboratoire de Recherches Cerebrovasculaires, CNRS UA 641, Université Paris VII, France.
S E
SE
Akopov
R
R
Sercombe
J
J
Seylaz
D000818:Animals; D002536:Cerebral Arteries / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D002546:Ischemic Attack, Transient; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009994:Osmolar Concentration; D010974:Platelet Aggregation; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate