Mast cell chymase-like protease(s) modulates Escherichia coli lipopolysaccharide-induced vasomotor dysfunction in skeletal muscle in vivo.
This study investigated whether short-term exposure to Escherichia coli lipopolysaccharide (LPS) elicits vasomotor dysfunction in skeletal muscle in vivo and, if so, whether perivascular mast cell proteases partly modulate this response. With intravital microscopy, we found that suffusion of E. coli LPS on the in situ hamster spinotrapezius muscle for 60 min elicits immediate vasoconstriction followed by vasodilation. Vasoconstriction is abrogated by SK&F 108566, a selective, nonpeptide angiotensin II (AT II) subtype 1 receptor antagonist, chymostatin and soybean trypsin inhibitor. These compounds also attenuate E. coli LPS-induced vasodilation. By contrast, superoxide dismutase, catalase and indomethacin attenuate only E. coli LPS-induced vasodilation. Endothelin receptor antagonists, lisinopril, leupeptin, Bestatin and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid are ineffective. Histochemical analysis of the spinotrapezius muscle reveals abundant perivascular mast cells with chymostatin-inhibitable chymase-like activity. Pretreatment of hamsters with compound 48/80 for 4 days curtails E. coli LPS-induced vasoconstriction and converts vasodilation to vasoconstriction. On balance, these data indicate that E. coli LPS stimulates perivascular mast cells in the in situ hamster spinotrapezius muscle to release an AT II-producing chymase-like protease(s). AT II thus produced elicits local vasoconstriction and elaborates reactive oxygen species which, in turn, generate vasodilator prostaglandins.
Suzuki
H
H
Department of Medicine, University of Illinois at Chicago, USA.
Caughey
G H
GH
Gao
X P
XP
Rubinstein
I
I
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D053818:Chymases; D006224:Cricetinae; D004926:Escherichia coli / Q000472:pathogenicity*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008407:Mast Cells / Q000201:enzymology / Q000502:physiology*; D008647:Mesocricetus; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D012697:Serine Endopeptidases / Q000502:physiology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects*
D008070:Lipopolysaccharides; D011453:Prostaglandins; D000804:Angiotensin II; D013482:Superoxide Dismutase; D012697:Serine Endopeptidases; D053818:Chymases