Journal of Nippon Medical School: Vol.69 No.1 page.013

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ArticleTitle Effect of L-canavanine, an Inhibitor of Inducible Nitric Oxide Synthase, on Myocardial Dysfunction During Septic Shock

AuthorList Norihito Suzuki, Atsuhiro Sakamoto and Ryo Ogawa

Affiliation Department of Anesthesiology, Nippon Medical School

Language EN

Volume 69

Issue 1

Year 2002

Page 13-18

Received June 5, 2001

Accepted June 28, 2001

Keywords nitric oxide (NO), nitric oxide (NO) synthase, working heart, L-canavanine, N^G-nitro-L-arginine methyl ester (L-NAME)

Abstract Overproduction of nitric oxide (NO) by inducible NO synthase (iNOS) plays a role in the pathophysiology of septic shock. The depression of cardiac contractility in such situations is mediated by proinflammatory cytokines, including interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). The effects of two NOS inhibitors with different isoform selectivity were compared in isolated working rat hearts. The depression of contractility by IL-1β and TNF-α was prevented by administration of a nonselective nitric oxide synthase inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME) or an inhibitor of inducible nitric oxide synthase, L-canavanine. In contrast, when L-NAME was administered in the absence of IL-1β and TNF-α, it depressed contractility over the 2h perfusion period by significantly reducing coronary flow. These results support current thinking that the depression of myocardial function by IL-1β and TNF-α is mediated, at least in part, by an intracardiac increase in inducible nitric oxide synthase, and that in contrast to L-NAME, the decline in coronary conductance seen in cytokine-treated is not prevented by L-canavanine hearts. L-canavanine shows selective inhibition of inducible nitric oxide synthase unlike the vasopressor action of L-NAME in cytokine-treated hearts.

Correspondence to Department of Anesthesiology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
norihito@nms.ac.jp

ArticleTitle	Effect of L-canavanine, an Inhibitor of Inducible Nitric Oxide Synthase, on Myocardial Dysfunction During Septic Shock
AuthorList	Norihito Suzuki, Atsuhiro Sakamoto and Ryo Ogawa
Affiliation	Department of Anesthesiology, Nippon Medical School
Language	EN
Volume	69
Issue	1
Year	2002
Page	13-18
Received	June 5, 2001
Accepted	June 28, 2001
Keywords	nitric oxide (NO), nitric oxide (NO) synthase, working heart, L-canavanine, N^G-nitro-L-arginine methyl ester (L-NAME)
Abstract	Overproduction of nitric oxide (NO) by inducible NO synthase (iNOS) plays a role in the pathophysiology of septic shock. The depression of cardiac contractility in such situations is mediated by proinflammatory cytokines, including interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). The effects of two NOS inhibitors with different isoform selectivity were compared in isolated working rat hearts. The depression of contractility by IL-1β and TNF-α was prevented by administration of a nonselective nitric oxide synthase inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME) or an inhibitor of inducible nitric oxide synthase, L-canavanine. In contrast, when L-NAME was administered in the absence of IL-1β and TNF-α, it depressed contractility over the 2h perfusion period by significantly reducing coronary flow. These results support current thinking that the depression of myocardial function by IL-1β and TNF-α is mediated, at least in part, by an intracardiac increase in inducible nitric oxide synthase, and that in contrast to L-NAME, the decline in coronary conductance seen in cytokine-treated is not prevented by L-canavanine hearts. L-canavanine shows selective inhibition of inducible nitric oxide synthase unlike the vasopressor action of L-NAME in cytokine-treated hearts.
Correspondence to	Department of Anesthesiology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan norihito@nms.ac.jp