Cultured endothelial cells restore vasodilator responses to coronary arteries with impaired endothelial function and alter the response to a nitric oxide donor.
The objective of this investigation was to determine the effect of cultured human umbilical vein endothelial cells (HUVEC) on the vascular response to canine coronary arteries in which the endothelium had been either mechanically removed or injured by multiple brief episodes of occlusion and reperfusion in vivo. The endothelium-dependent vasodilator, A23187 (10(-6) mol/l) did not cause any significant relaxation in vessels from which the endothelium had been removed. However, following addition of cultured HUVEC to the tissue bath (75 x 10(3) cells/ml), A23187 produced a significant (p < 0.05) relaxation. This effect was abolished by inhibition of nitric oxide synthase with Nw-nitro-l-arginine methyl ester (L-NAME). Vascular relaxation caused by the nitric oxide donor SIN-1 was significantly (p < 0.05) enhanced when cultured HUVEC were added to vessels mechanically denuded of endothelium. Repetitive ischemia and reperfusion significantly inhibited the relaxant response to A23187. Addition of cultured HUVEC to the tissue bath partially restored the response to A23187. In contrast to the mechanically damaged vessels the relaxant response to SIN-1 was unaffected by cultured HUVEC in reperfusion-injured vessels. These results demonstrate that cultured endothelial cells partially restore endothelium-dependent vasodilation of vessels in which the endothelium is not functional following mechanical- or reperfusion-induced damage. The differential effect of endothelial cells on the response to SIN-1 suggests that mechanical and reperfusion injury alter the coronary vascular response to SIN-1 by different mechanisms.
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
D
D
Kenny
M G
MG
Coughlan
J P
JP
Kampine
R R
RR
Montgomery
Z J
ZJ
Bosnjak
D C
DC
Warltier
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009569:Nitric Oxide; D000001:Calcimycin; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D019331:NG-Nitroarginine Methyl Ester