AJP - Heart and Circulatory Physiology, Vol 258, Issue 3 848-H853, Copyright © 1990 by American Physiological Society
Chemotactic peptide FMLP contracts human coronary arteries via cyclooxygenase products
S. M. Bode, M. Kuhn and U. Forstermann
Department of Clinical Pharmacology, Hannover Medical School, Federal Republic of Germany.
The chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine
(FMLP) is a constrictor of bronchial smooth muscle. Recently it has also
been shown to contract rabbit coronary arteries by an unknown mechanism.
This prompted us to investigate whether the chemotactic peptide has an
effect on the tone of human coronary arteries obtained during heart
transplantation. FMLP was found to be a potent and efficacious myotropic
agent on strips of human coronary artery. Contractions were generally
transient and subject to tachyphylaxis. The FMLP-induced vasoconstriction
was not dependent on the presence of endothelial cells. The response was
unaffected by the histamine H1-antagonist diphenhydramine or the antagonist
of peptido-leukotrienes FPL 55712. However, the contractions were
completely abolished in the presence of the fatty acid cyclooxygenase
inhibitors aspirin or indomethacin. Stimulation of rings of human coronary
artery with FMLP resulted in a marked production of prostaglandin (PG)F2
alpha, a smaller production of PGD2, and a slight increase in thromboxane
B2. All these prostanoids constricted the artery, but the stable
thromboxane mimetic U44069 was 100 times more potent than PGF2 alpha or
PGD2. These data indicate that FMLP activates cells of unknown identity in
the adventitia or media of human coronary arteries to produce a mixture of
vasoconstrictor cyclooxygenase products. These compounds are likely to
mediate the myotropic effect of FMLP on this artery. The mechanism may
participate in the pathogenesis of some forms of coronary vasospasm.
