Effects of l-Canavanine and ozone on vascular reactivity in septicemic rats

Abstract

Septicemia leads to oxidative stress with overproduction of reactive-oxygen species (ROS) and consumption of endogenous antioxidant enzymes. We tested a twofold hypothesis: (1) does oxidative stress (OxS) induced by sepsis acting alone or in concert with augmented inflammatory processes contributes to sepsis-related vascular dysfunction, and, (2) whether ozone (O(3)) and L-canavanine (CAV) mitigate the negative impact of the aforementioned phenomena. We investigated the relative impact of treatment with CAV and/or O(3) on vascular OxS associated vascular functional changes in septicemic rats. For this study, 60 male Sprague-Dawley rats were used and divided into six experimental groups (n = 10): control group (C), sham-operated (Sham), septicemic rats (S), S rats treated with CAV (100 mg/kg. i.p; S + CAV), S rats treated with O(3) (1.2 mg/kg, i.p.; S + O(3)) and S rats treated with both O(3) and CAV (S + O(3) + CAV). After 22 h, the mean arterial blood pressure (MAP), the aortic ring vascular reactivity to phenylephrine, abdominal aortic blood flow (AABF), serum tumor necrosis factor-alpha (TNF-alpha) and plasma nitrite/nitrate (NOx) concentration were measured. In addition, hepatic antioxidant enzyme activities sodium dismutase (SOD) and glutathione peroxidase (GSH-Px) were estimated. Septicemia caused significant elevation of serum TNF-alpha (p < 0.001) and plasma NOx (p < 0.001) and significant (p < 0.001) reduction of AABF (p < 0.001), aortic vascular response to phenylephrine (p < 0.001), MAP (p < 0.001) and hepatic SOD and GSH-Px activity (p < 0.001) compared with the C group, while treatment with O(3) and/or CAV induced significant amelioration of all those increases. Abnormalities were attenuated to a similar extent with treatment with both O(3) and CAV. These results suggested that concomitant administration of O(3) and CAV alleviated the compromised vascular reactivity in septicemic conditions and prevent its progression into septic shock compared with each alone.