Activated human polymorphonuclear leukocytes elicit endothelium-dependent contraction in isolated pig coronary arteries.
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.
Murohara
T
T
Division of Cardiology, Kumamoto University School of Medicine, Japan.
Kugiyama
K
K
Sugiyama
S
S
Ohgushi
M
M
Yasue
H
H
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D003331:Coronary Vessels / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005609:Free Radicals; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008163:Luminescent Measurements; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology; D013552:Swine; D015054:Zymosan / Q000494:pharmacology; D019323:omega-N-Methylarginine
D016227:Benzoquinones; D005609:Free Radicals; D016859:Lipoxygenase Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D015054:Zymosan; D001120:Arginine; D013482:Superoxide Dismutase; D007213:Indomethacin