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Nitric Oxide in Cirrhosis
- Jaye P.F. Chin-Dusting, PhD; and
- Brindi Rasaratnam, MBBS
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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.
Jaye P.F. Chin-Dusting, PhD
Baker Medical Research Institute; Victoria, Australia
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
