[Cholecystokinin-octapeptide alleviates tumor necrosis factor-alpha induced changes in rabbit pulmonary arterial reactivity and injuries of endothelium in vitro].
To explore the mechanism underlying cholecystokinin-octapeptide (CCK-8) induced attenuation of pulmonary arterial hypertension (PAH) in endotoxic shock, the effects of CCK-8 on the changes in rabbit pulmonary arterial reactivity induced by tumor necrosis factor-alpha (TNF-alpha) were observed with the isolated arterial ring technique, and the ultrastructure of pulmonary arterial endothelium was observed under a scanning electron microscope. The contractile response to -adrenoceptor agonist phenylephrine (PE), the endothelium-dependent relaxation response to acetylcholine (ACh) and the endothelium-independent relaxation response to sodium nitroprusside (SNP) were not affected by TNF-alpha (4000 U/ml) after incubation for 2 h, while, if the incubation time was prolonged to 7 or 14 h, the relaxation response of pulmonary artery to ACh was depressed significantly, which, however, could be reversed by concomitant exposure to CCK-8 (0.5 microgram/ml). Incubation of pulmonary artery with CCK-8 (0.5 microgram/ml) alone did not bring out any contractile responses. Moreover, CCK-8 (0.5 microgram/ml) alleviated the ultrastructural lesions induced by TNF-alpha (4000 U/ml). These results suggest that CCK could protect pulmonary arterial endothelium against the detrimental effects by TNF-alpha.
Meng
A H
AH
Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, China.
Ling
Y L
YL
Wang
D H
DH
Gu
Z Y
ZY
Li
S J
SJ
Zhu
T N
TN
D000818:Animals; D004730:Endothelium, Vascular / Q000648:ultrastructure*; D005260:Female; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D011651:Pulmonary Artery / Q000502:physiology* / Q000648:ultrastructure; D011817:Rabbits; D012844:Sincalide / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014664:Vasodilation / Q000187:drug effects
D014409:Tumor Necrosis Factor-alpha; D012844:Sincalide