Multiple factors contributing to lipopolysaccharide-induced reactivity changes in rabbit pulmonary artery.
To explore the underlying mechanism(s) of pulmonary arterial hypertension in endotoxic shock, the roles of N-acetylcysteine (NAC), nitric oxide (NO) and carbon monoxide (CO) were investigated. Pulmonary arterial rings (3-mm width) were prepared from 24 rabbits. Lipopolysaccharide (LPS), after 7-hour incubation, decreased the endothelium-dependent relaxation response of the arterial ring (pre-contracted with phenylephrine) to acetylcholine (1 mumol/L), but did not affect the endothelium-independent relaxation response to sodium nitroprusside. The LPS effects were reduced by a concomitant incubation with the free radical scavenger (NAC), NO donor (L-arginine), and CO donor (hemin), respectively. On the other hand, the LPS effects were enhanced by applying heme oxygenase-1 (HO-1) inhibitor (zinc protoporphyrin) to block CO production. The response to acetylcholine changed from relaxation to contraction, however, the contractile response to phenylephrine increased significantly after pre-incubation with nitric oxide synthase (NOS) inhibitor (L-NAME) to block NO production, confirming the importance of CO and NO. These results show that LPS impairs endothelium-dependent relaxation of the pulmonary artery, which can be greatly reduced by the antioxidant, or by supplying with NO and CO. Thus, multiple factors are involved in this model of endotoxin-induced pulmonary hypertension.
Huang
Xin-Li
XL
Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, China.
Ling
Yi-Qun
YQ
Zhu
Tie-Nian
TN
Zhang
Jun-Lan
JL
Ling
Yi-Ling
YL
D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D011817:Rabbits; D012772:Shock, Septic / Q000150:complications*
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D002248:Carbon Monoxide; D000111:Acetylcysteine