Open AccessActivated Human Polymorphonuclear Leukocytes Elicit Endothelium-Dependent Contraction in Isolated Pig Coronary Arteries
Author(s) -
Toyoaki Murohara,
Kiyotaka Kugiyama,
Seigo Sugiyama,
Masamichi Ohgushi,
Hirofumi Yasue
Publication year - 1993
Publication title -
journal of cardiovascular pharmacology
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-199305000-00011
Subject(s) - contraction (grammar) , superoxide , endothelium , nitric oxide , medicine , chemistry , superoxide dismutase , prostacyclin , endocrinology , prostaglandin , zymosan , omega n methylarginine , nitric oxide synthase , biochemistry , oxidative stress , in vitro , enzyme
Interaction between activated human polymorphonuclear leukocytes (PMNL) and endothelial regulation of isolated pig coronary artery tone was examined. PMNL were isolated from venous blood of healthy human volunteers. Pig coronary artery rings were incubated in an organ chamber, and isometric tension changes induced by opsonized zymosan (1 mg/ml)-activated PMNL were examined. Activated PMNL elicited dose-dependent contraction (maximum value 45.9 +/- 4.1% of precontraction, mean +/- SEM] in prostaglandin F2 alpha (PGF2 alpha)-precontracted rings. The contraction was markedly attenuated by superoxide dismutase (SOD 100 U/ml) to 9.9 +/- 2.4% (p < 0.001), but not by catalase (1,000 U/ml). After inhibition of basal production of endothelium-derived relaxing factor (EDRF) (nitric oxide, NO) by endothelial removal or by treatment of an inhibitor of NO synthase, NG-monomethyl-L-arginine (L-NMMA), PMNL also failed to induce the contraction. A 5-lipoxygenase inhibitor (AA-861) and a cyclooxygenase inhibitor (indomethacin) did not alter the contraction to activated PMNL significantly. Time course of oxygen free radical release from PMNL measured by luminol-dependent chemiluminescence was closely synchronized with that of the endothelium-dependent contraction elicited by PMNL. In each preparation of PMNL, the maximum luminescence count and the maximum contraction induced by activated PMNL showed significant positive correlation quantitatively (r = 0.958, p < 0.001). Activated human PMNL elicited endothelium-dependent contraction in isolated pig coronary arteries. The contraction may be mediated through inactivation of basal production of EDRF (NO) by superoxide anions released from PMNL.