Effects of leukotrienes C4 and D4 on human isolated saphenous veins.
1. Vascular injury during the intra-operative procedures of bypass surgery may be the initiating event in the gradual deterioration in the patency of the graft. Adhesion of leukocytes to the vascular endothelium frequently accompanies preparation and insertion of the graft. However, little is known about the effects of vasoactive substances released from leukocytes on vein graft performance. 2. To determine whether leukotrienes are capable of affecting the tone of blood vessels used as coronary artery bypass grafts we studied the human saphenous vein as intact rings using an isolated organ bath technique. 3. LTC4 and LTD4 caused weak endothelium-dependent relaxations at lower concentrations (1 pM to 1 nM) and powerful endothelium-independent contractions at higher concentrations (3 nM to 0.1 microM). The maximum responses to LTC4 and LTD4 for relaxations were 21.1 +/- 4.8% and 28.6 +/- 3.4% (% of noradrenaline induced tone) respectively and 64.6 +/- 9.9% and 59.1 +/- 7.9% (% response to KCl) respectively for contractions. 4. The inhibitor of nitric oxide formation, L-NG-monomethyl L-arginine, prevented the relaxations to LTD4, but not LTC4 and unmasked endothelium-dependent contractions to LTD4 (32.9 +/- 11.3%). NG-monomethyl L-arginine had no effect on the contractions produced by LTC4 or LTD4. 5. Indomethacin augmented relaxations and contractions of saphenous vein to LTC4 from 22.5 +/- 5.6 to 40.02 +/- 8.7 (P < 0.05) and 48.8 +/- 5.5% to 74.7 +/- 7.6% (P < 0.01) respectively. LTD4 responses were not affected by indomethacin treatment. 6. In conclusion, leukotrienes mediate biphasic responses in the human saphenous vein.(ABSTRACT TRUNCATED AT 250 WORDS)
Allen
S P
SP
National Heart and Lung Institute, Harefield Hospital, Middlesex, UK.
Chester
A H
AH
Piper
P J
PJ
Sampson
A P
AP
Akl
E S
ES
Yacoub
M H
MH
D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D013189:SRS-A / Q000494:pharmacology*; D012501:Saphenous Vein / Q000187:drug effects; D019323:omega-N-Methylarginine
D013189:SRS-A; D019323:omega-N-Methylarginine; D001120:Arginine