Chronic endotoxemia and endothelium-dependent vasodilation in coronary arteries.
Endotoxin acutely decreases the production of nitric oxide, leading to abnormal regulation of coronary vascular tone: however, the effects of chronic endotoxemia on vasomotion are unknown. We therefore tested the hypothesis that chronic, low-level endotoxemia inhibits endothelium-dependent vasodilation. Rabbits were continuously infused with a subclinical dose of Escherichia coli endotoxin (.6 microgram/24 h, intraperitoneal) or saline for 5 wk. Endotoxin at this concentration elicited no significant sustained pyretic or hemodynamic responses. Both endothelium-dependent and independent vasomotor responses were determined in coronary arteries (250-500 mu). Vasorelaxation in response to acetylcholine, but no adenosine diphosphate (ADP), was significantly enhanced in endotoxin-challenged animals (EC50 = 62.6 +/- 11.1 nM, control vs. 33.97 +/- 5.7 nM, endotoxin-challenged; p < .05). Vasoconstriction to PGF2 alpha, but not KCl, was significantly decreased in endotoxin-challenged animals. These results indicate that endothelium-dependent and independent vasomotor responses are altered during chronic endotoxemia and are due, in part, to alterations in signal-transduction mechanisms specific for certain types of receptors.
Dalton Cardiovascular Research Center, Department of Physiology, University of Missouri, Columbia 65211, USA.
P R
PR
Myers
M
M
Gupta
S
S
Rogers
M L
ML
Mattox
H R
HR
Adams
J L
JL
Parker
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature; D001835:Body Weight; D002908:Chronic Disease; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D019446:Endotoxemia / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D019323:omega-N-Methylarginine; D000244:Adenosine Diphosphate; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester