L-canavanine, a selective inhibitor of inducible NO synthase, increases plasma endothelin-1 concentrations in dogs with endotoxic shock.

Abstract

PURPOSE:

The purpose of this article is to elucidate the effect of L-canavanine, a selective inhibitor of inducible NO synthase (iNOS), on hemodynamics, blood gas parameters, and plasma concentrations of lactate and endothelin-1 (ET-1) during endotoxic shock.

MATERIALS AND METHODS:

Eleven mongrel dogs under pentobarbital anesthesia were divided into two groups: (1) bacterial lipopolysaccharide (LPS) plus vehicle group (n = 5) receiving infusion of LPS (3 mg/kg/h for 1 h) followed by vehicle (2 mL/h for 5 hours); (2) LPS plus L-canavanine group (n = 6) receiving infusion of LPS (3 mg/kg/h for 1 hour) followed by L-canavanine (10 mg/kg/h for 5 hours).

RESULTS:

LPS caused a significant (P < .05) decrease in mean arterial pressure (MAP) at 1 hour, but there was no significant difference in MAP during 6-hour period between the two groups. LPS alone did not cause significant changes in other hemodynamics, whereas L-canavanine caused a significant (P < .05) increase in pulmonary vascular resistance index (PVRI) and a decrease in oxygen delivery at 6 hours. The LPS-induced lactic acidosis and hypersecretion of ET-1 were aggravated after L-canavanine infusion. Plasma ET-1 showed positive correlations to lactate levels and PVRI, and negative correlations to cardiac output and oxygen delivery only in the LPS plus L-canavanine group, but not in the LPS plus vehicle group.

CONCLUSIONS:

This study suggests that L-canavanine induces tissue hypoperfusion and ischemia with concomitant hypersecretion of ET-1 in dogs with endotoxic shock.

• Authors: C Mitaka, Y Hirata, K Yokoyama, T Imai
• Journal: Journal of critical care (J Crit Care) Vol. 16 Issue 1 Pg. 17-23 (Mar 2001) ISSN: 0883-9441 [Print] United States
• PMID: 11230720 (Publication Type: Journal Article)

Chemical References

• Endothelin-1
• Enzyme Inhibitors
• Lactic Acid
• Canavanine
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II

Topics

• Animals
• Blood Gas Analysis
• Canavanine (pharmacology)
• Disease Models, Animal
• Dogs
• Endothelin-1 (blood)
• Enzyme Inhibitors (pharmacology)
• Hemodynamics
• Lactic Acid (blood)
• Male
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitric Oxide Synthase Type II
• Shock, Septic (blood)