NITRIC OXIDE SCAVENGING MODULATES AN EXPERIMENTAL VASOPLESIA IN-VITRO
| Autor: | J. Tai, Greenburg Ag, Hae Won Kim |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Lipopolysaccharides
Male medicine.medical_specialty Lipopolysaccharide Biomedical Engineering Nitric Oxide Nitric oxide Rats Sprague-Dawley Norepinephrine (medication) Hemoglobins Norepinephrine chemistry.chemical_compound Internal medicine medicine Animals Aorta Dose-Response Relationship Drug biology Septic shock Drug Synergism Free Radical Scavengers medicine.disease Rats Vasodilation Nitric oxide synthase NG-Nitroarginine Methyl Ester Endocrinology chemistry Vasoconstriction Enzyme inhibitor Shock (circulatory) biology.protein Blood Vessels Hemoglobin medicine.symptom Biotechnology medicine.drug |
| Zdroj: | Artificial Cells, Blood Substitutes, and Biotechnology. 29:263-274 |
| ISSN: | 1532-4184 1073-1199 |
| Popis: | Endogenous overproduction of nitric oxide (NO) is believed to be a primary cause of refractory hypotension in septic shock. Under this condition, effectiveness of vasopressors is diminished due to hyporeactivity of blood vessels, a condition termed as vasoplesia. Effective reduction of NO levels should alleviate the condition. In this study, we investigated whether NO scavenging could modulate the endotoxin mediated vasoplesia in-vitro. Further, we explored whether NO scavenging in combination with a moderate NO synthase (NOS) inhibition would also be effective in modulating NO mediated vasoplesia. Experimental vasoplesia was produced in-vitro by incubating isolated rat thoracic aortic rings with lipopolysaccharide (LPS). Vessel rings were then treated with N(omega)-nitro-L-arginine methyl ester (L-NAME; a NOS inhibitor), human hemoglobin (Hb; a NO scavenger), or both L-NAME and Hb. Vascular reactivity was assessed by measuring vessel ring isometric tension changes to norepinephrine (NE) doses; the median effective doses (logEC50) of NE before and after each experimental treatment were compared. Following a 6-hour LPS treatment, vascular reactivity logEC50 values for NE were significantly increased compared with control vessel rings incubated without LPS. Treatment with either L-NAME alone or Hb alone significantly improved the vessel ring reactivity to NE. When both L-NAME and Hb were used concomitantly, vascular reactivity was also significantly improved. These results indicate that NO scavenging with Hb is as effective as NO synthesis inhibition with NAME in modulating the endotoxin induced vasoplesia. In conclusion, NO scavenging, alone or in combination with a moderate NOS inhibition, may render an alternative therapeutic approach to NOS synthesis inhibition in modulating the vasoplesia in septic shock. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|