Role of nitric oxide in a nonseptic shock model induced by zymosan in the rat.

Abstract

Nitric oxide (NO) is a short-lived mediator, the synthesis of which is induced by various cytokines during inflammatory processes. Recently, it has been proposed that zymosan, a nonbacterial agent, causes inflammation by inducing the production of various cytokines and proinflammatory mediators. In the present study we investigated the role of NO in a nonseptic shock model induced by zymosan administration in the rat. Administration of zymosan (500 mg/kg, intraperitoneally) in the rat induced acute peritonitis, as assessed by a marked increase in the leukocytes count in the exudate, as well as by an increase in the exudate nitrate/nitrite concentration. Zymosan-treated rats developed a severe hypotension and showed signs of systemic illness, significant loss of body weight, and a high mortality rate (53% of animals died within 72 h). Elevated plasma levels of nitrite and nitrate were also observed in zymosan-treated rats compared with control rats (67 +/- 4 microM and 23 +/- 2 microM, respectively; p < .01). In ex vivo experiments, vascular reactivity was studied in thoracic aorta rings of zymosan-treated rats. The contractile responses to norepinephrine (100 nM) and endothelin-1 (5 nM) were significantly reduced. An impairment of the endothelial-dependent relaxation in response to acetylcholine was also observed. Pretreatment of zymosan-shocked rats with NG-nitro-L-arginine methyl ester (L-NAME) or NG-monomethyl-L-arginine (L-NMA), (10 mg/kg, subcutaneously, 15 min before zymosan) decreased mortality, prevented the development of peritonitis, improved ex vivo vascular reactivity, and significantly reduced hypotension. Our data suggest that overproduction of NO plays a role in the zymosan-induced peritonitis and cardiovascular derangements in the rats.

• Authors: S Cuzzocrea, A Filippelli, B Zingarelli, M Falciani, A P Caputi, F Rossi
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 7 Issue 5 Pg. 351-7 (May 1997) ISSN: 1073-2322 [Print] United States
• PMID: 9165670 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Nitrates
• Nitrites
• Nitric Oxide
• Zymosan

Topics

• Acute Disease
• Animals
• Ascitic Fluid (metabolism)
• Blood Pressure (drug effects)
• Cardiovascular Diseases (chemically induced, physiopathology)
• Enzyme Inhibitors (pharmacology)
• Male
• Nitrates (blood, metabolism)
• Nitric Oxide (physiology)
• Nitrites (blood, metabolism)
• Peritonitis (chemically induced, physiopathology)
• Rats
• Rats, Sprague-Dawley
• Shock (chemically induced, physiopathology)
• Vasomotor System (drug effects)
• Zymosan (toxicity)