Endothelium and the effect of activated neutrophils on arterial smooth muscle

The aim of the study was to analyze the involvement of the endothelium in the effects of neutrophils (PMNL) on phenylephrine-precontracted isolated rings of the rat thoracic aorta and to compare their effects with those of peroxynitrite (ONOO(−)) and hypochlorous acid (HOCl). Activated PMNL-induced contraction of the precontracted aorta was prevented by the blockade of NO-synthase and by endothelium removal. In the endothelium-free preparations, the effect of PMNL reappeared in the presence of sodium nitroprusside. The effect of ONOO(–) and HOCl significantly differed from that of activated PMNL both in the presence and absence of the endothelium. It is therefore likely that neither ONOO(–) nor HOCl generated by transformation of superoxide anion radical (O(2)(•–)) produced by PMNL is involved in their action. Reduction of the relaxant effect of nitric oxide derived from the endothelium by O(2)(•–) seems to be the keystone mechanism in generation of PMNL-induced contraction.