Effect of L-NAME on nitric oxide and gastrointestinal motility alterations in cirrhotic rats.
OBJECTIVE
To investigate the effect of L-NAME on nitric oxide and gastrointestinal motility alterations in cirrhotic rats.


METHODS
Rats with cirrhosis induced by carbon tetrachloride were randomly divided into two groups, one n =13 receiving 0.5mg.kg(-1) per day of N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, for 10 days, whereas the other group (n =13) and control (n =10) rats were administrated the same volume of 9g.L(-1) saline. Half gastric emptying time and 2h residual rate were measured by SPECT, using (99m)Tc-DTPA-labeled barium sulfate as test meal. Gastrointestinal transition time was recorded simultaneously. Serum concentration of nitric oxide (NO) was determined by the kinetic cadmium reduction and colorimetric methods. Immunohistochemical SABC method was used to observe the expression and distribution of three types of nitric oxide synthase (NOS) isoforms in the rat gastrointestinal tract. Western blot was used to detect expression of gastrointestinal NOS isoforms.


RESULTS
Half gastric emptying time and trans-gastrointestinal time were significantly prolonged(124.0 +/- 26.4 min; 33.7 +/- 8.9 min; 72.1 +/- 15.3 min; P<0.01), (12.4 +/- 0.5h; 9.5 +/- 0.3h; 8.2 +/- 0.8h; P<0.01), 2h residual rate was raised in cirrhotic rats than in controls and cirrhotic rats treated with L-NAME (54.9 +/- 7.6%,13.7 +/- 3.2%, 34.9 +/- 10.3%, P<0.01). Serum concentration of NO was significantly increased in cirrhotic rats than in the other groups (8.20 +/- 2.48) micromol.L(-1), (5.94 +/-1.07) micromol.L(-1) and control (5.66 +/- 1.60 micromol.L(-1), P<0.01. NOS staining intensities which were mainly located in the gastrointestinal tissues were markedly lower in cirrhotic rats than in the controls and cirrhotic rats after treated with L-NAME.


CONCLUSIONS
Gastrointestinal motility was remarkably inhibited in cirrhotic rats, which could be alleviated by L-NAME. Nitric oxide may play an important role in the inhibition of gastrointestinal motility in cirrhotic rats.
Wang
Xin
X
Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710033, Shaanxi Province, China.
Zhong
Yue-Xia
YX
Zhang
Zong-You
ZY
Lu
Ju
J
Lan
Mei
M
Miao
Ji-Yan
JY
Guo
Xue-Gang
XG
Shi
Yong-Quan
YQ
Zhao
Yan-Qiu
YQ
Ding
Jie
J
Wu
Kai-Cun
KC
Pan
Bo-Rong
BR
Fan
Dai-Ming
DM
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D004064:Digestive System / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011859:Radiography; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015899:Tomography, Emission-Computed, Single-Photon
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D002251:Carbon Tetrachloride; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester