The relationship of endothelin-1 and inducible nitric oxide synthase at several stages of the anastomotic healing process.
OBJECTIVE
The aim of this study was to investigate the interaction between the endothelin-1 (ET-1) and inducible NO synthase (iNOS) in anastomotic healing.


METHODS
The expression of ET-1 and iNOS were investigated by immunohistochemistry in a rat end-to-end arterial anastomotic model. The aorta of 50 male Wistar rats was exposed, then transversely divided and re-anastomosed. The animals were sacrificed immediately after the operation (group A, control group), after 24 h (group B), on 7th postoperative day (group C), on 30th day (group D) and at 6 months (group E). Intima and media thickness and their ratio of the anastomotic segments in each group were calculated from computer digitized images of the individual sections. ET-1 and iNOS expression were measured on a semiquantitative scale ranging from 0 to 3.


RESULTS
ET-1 was expressed from endothelial and smooth muscle cells (SMCs), while iNOs was expressed from SMCs and inflammatory cells. An intense expression of ET-1 was demonstrated mainly at 1 week and to a lesser degree at 1 month. Yet, at 6 months this expression was significantly weakened (P<0.001). In contrast, an intense iNOS expression was identified at 24 h, substantially regressing at statistical significant lower levels after 1 week (P<0.001). Bivariate correlation test showed a positive correlation between ET-1 and iNOS expression.


CONCLUSIONS
ET-1 appears to play an important role in intimal thickening during anastomotic healing, especially in the late period of the process. Although there is a positive correlation between ET-1 and iNOS production, the activity of the latter is relatively limited after the first postanastomosis week.
Papalambros
K E
KE
1st Department of Surgery, Medical School, University of Athens, Athens, Greece. sgeorg@med.uoa.gr
Sigala
F
F
Georgopoulos
S
S
Kavantzas
N
N
Panou
N
N
Sigalas
K
K
Felekouras
E
E
Papalambros
A L
AL
Giannopoulos
A
A
Aesopos
A
A
Bastounis
E
E
D000714:Anastomosis, Surgical; D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000503:physiopathology / Q000601:surgery*; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000201:enzymology; D007150:Immunohistochemistry; D008297:Male; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014656:Vascular Surgical Procedures; D014945:Wound Healing
D019332:Endothelin-1; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat