REPLY
Nitric Oxide in Cirrhosis
Jaye P.F. Chin-Dusting, PhD, and
Brindi Rasaratnam, MBBS
15 June 1998 | Volume 128 Issue 12 Part 1 | Pages 1046-1047
IN RESPONSE:
We agree that endotoxin (and NO) may be only partly responsible for the findings we observed. It is also likely that the cardiovascular abnormalities stem from many mechanisms and that they depend on disease severity. In a previous study of cirrhotic patients with normal basal forearm blood flow, responses to acetylcholine were significantly attenuated [1]. This finding occurred concurrently with evidence that smooth muscle-derived NO concentrations were elevated. Responses to the NO synthase inhibitor NG -monomethyl-L-arginine (L-NMMA) were unaffected. In our study, the patients exhibited increased peripheral vasodilation, enhanced responses to L-NMMA and acetylcholine, and increased plasma nitrite and nitrate levels. Only basal forearm blood flow and responses to L-NMMA were normalized by norfloxacin. Thus, although we recognize that responses to endothelium receptor-dependent agonists such as acetylcholine are attenuated in vessels exposed to cytokines [2], we contend that the enhanced responses to acetylcholine seen in the cohort we studied occurred independently of the endotoxemia of these patients.
As Dr. Pastor rightly points out, the findings of an enhanced response to a muscarinic agonist in cirrhotic patients is not new. Clearly, mechanisms other than the endotoxin-NO cascade play a role. One possibility is that the increased response to acetylcholine is a consequence of the increased levels of estradiol normally reported in these patients [3, 4]. With regard to the concerns about plasma nitrite and nitrate levels, again it is unlikely that the elevation we observed is due to the endotoxemia because these levels were unaffected by norfloxacin. The difference in scale of these levels may, for example, reflect the degree of renal failure and hence clearance of these nitrosylated compounds rather than NO production. Further investigations are warranted to define the vascular abnormalities of these patients.
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Author and Article Information
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Baker Medical Research Institute; Victoria, Australia
Alfred Hospital; Victoria, Australia
1. Ryan J, Jennings G, Dudley F, Chin-Dusting J. Smooth muscle derived nitric oxide is elevated in isolated forearm veins in human alcoholic cirrhosis. Clin Sci. 1996; 91:23-8.
2. Kessler P, Baucrsaxhs J, Busse R, Schini-Kerth VB. Inhibition of inducible nitric oxide synthase restores endothelium-dependent relaxations in proinflammatory mediator-induced blood vessels. Arterioscler Thromb Vasc Biol. 1997; 17:1746-55.
3. Farinati F, De Maria N, Marafin C, Fagiuoli S, Della Libera G, Naccarato R. Hepatocellular carcinoma in alcoholic cirrhosis: is sex hormone imbalance a pathogenetic factor? Eur J Gastroenterol Hepatol. 1995; 7:145-50.
4. Taddei S, Virdis A, Ghiadoni L, Mattei P, Sudano I, Berminin G, et al. Menopause is associated with endothelial dysfunction in women. Hypertension. 1996; 28:576-82.
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