Modulation of vascular tone of normal and arteriosclerotic arteries by leukocytes
Mügge, A.; Heublein, B.; Lichtlen, P.R.
Zeitschrift für Kardiologie 81(7): 361-377
1992
ISSN/ISBN: 0300-5860 PMID: 1509794 Document Number: 395001
Leukocytes, in particular mononuclear cells, play a central role in the pathogenesis of arteriosclerosis. The arteriosclerotic vessel wall is chemotactic for circulating leukocytes. Activated leukocytes are known to release a variety of vasoactive substances. Thus, activation of leukocytes in diseased arteries is not only an epiphenomenon of an inflammatory process, but instead may contribute to arteriosclerosis-associated complications such as vasoconstriction/vasospasm and thrombotic vessel occlusion. Influence of leukocytes on vascular tone appears to be complex and may be modulated by the presence of intact endothelium and additional blood constituents such as platelets. In vitro, mononuclear and polymorphonuclear leukocytes both relax and contract isolated arteries according to experimental conditions and leukocyte isolation protocols. In vivo, activation of leukocytes by chemotactic peptides f-met-leu-phe or complement C5a produces pronounced vasoconstriction. Mediators of these leukocyte-induced vascular responses are partially characterized and consist of nitric oxide (or EDRF-like factor), superoxide anions, thromboxane A2, peptidoleukotrienes, and an unknown contractile factor. In addition, leukocytes may indirectly modulate vascular tone by cleavage of angiotensin II from angiotensinogen or angiotensin I, and by inhibiting or stimulating platelet aggregation. Thus, leukocytes and their products may have several pathways to modulate vascular tone. Abnormal interactions between endothelium-platelet-leukocytes with vascular tone may play an important role in the pathogenesis of vascular complications in patients with coronary artery disease.