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The role of nitric oxide in subcutaneous and transmural gut tissue oxygenation
D D Zabel1, H W Hopf, T K Hunt
1Department of Surgery, Medical Center of Delaware, Wilmington, Delaware, USA.
Abstract:
The influence of inhibiting the nitric oxide (NO) synthetase on tissue perfusion as indicated by tissue oxygen tensions was determined. Tissue oxygen probes were placed subcutaneously and on serosal and mucosal surfaces of colon of anesthetized adult rats. After a control period, the inhibitor of NO formation, N(G)-nitro-L-arginine methyl ester (L-NMMA), was given intravenously and followed 20 min later by infusion of substrate for NO synthetase, L-arginine. Mean arterial blood pressure (MAP), subcutaneous tissue oxygen tension (P(SQ)O2), serosal tissue oxygen tension (P SO(2)), and mucosal tissue oxygen tension (P(M)O2) were simultaneously measured. Baseline values for the measured parameters were MAP = 95 + or - 9 mmHg, P(SQ)O2 = 61 + or - 7 mmHg, P(S)O2 65 + or - 7 mmHg, and P(M)02 = 9 + or - 2 mmHg. The infusion of L-NMMA induced a significant increase in MAP to 123 + or - 7 mmHg (p < .001) and P(SQ)O2 to 72 + or - 7 mmHg (p < .001). P(S)O2 did not change significantly from baseline after L-NMMA infusion. A significant decrease in P(M)O2 to 4 + or - 2 mmHg was noted after L-NMMA infusion (p < .001). The administration of L-arginine promptly returned all measured parameters to baseline levels within 10 min of infusion. A transmural P(O2) gradient exists across the colon with P(M)O2 far lower than P(S)O2. P(SQ)O2 approximates P(S)O2 at baseline and P(S)O2 is not altered by inhibition of the NO synthetase. The 45% reduction in mucosal PO2 after L-NMMA, which was reversed by L-arginine infusion, suggests that nitric oxide participates in splanchnic vasomotor control with a preferential effect in the mucosal vasculature. The observed decrease in mucosal PO2 observed after inhibition of NO production is similar to the worsened hypoxia previously measured during hemorrhagic shock. Further work clarifying the local control mechanisms of gut tissue P02 can direct therapies to increase gut tissue oxygenation.
Insights
Inhibiting nitric oxide (NO) synthetase significantly reduced mucosal oxygen tension in rats, indicating NO’s role in splanchnic vasomotor control. Restoring NO with L-arginine reversed this effect, highlighting its importance for gut oxygenation.
Area of Science:
- Physiology
- Pharmacology
- Gastroenterology
Background:
- Nitric oxide (NO) plays a crucial role in regulating blood flow and tissue oxygenation.
- Understanding the local control mechanisms of gut tissue oxygenation is vital for treating conditions like hemorrhagic shock.
Purpose of the Study:
- To investigate the influence of inhibiting nitric oxide (NO) synthetase on tissue perfusion, specifically measuring tissue oxygen tensions.
- To determine the role of NO in splanchnic vasomotor control and its preferential effect on mucosal vasculature.
Main Methods:
- Tissue oxygen probes were placed in rats to measure subcutaneous, serosal, and mucosal oxygen tensions.
- N(G)-nitro-L-arginine methyl ester (L-NMMA), an inhibitor of NO formation, was administered intravenously.
- L-arginine, a substrate for NO synthetase, was infused to observe its effect on reversing the inhibition.
Main Results:
- Inhibition of NO synthetase by L-NMMA significantly increased mean arterial blood pressure and subcutaneous oxygen tension.
- A significant decrease in mucosal oxygen tension was observed after L-NMMA administration.
- L-arginine infusion promptly restored all measured parameters to baseline levels.
Conclusions:
- Nitric oxide (NO) participates in splanchnic vasomotor control, with a preferential effect on the mucosal vasculature.
- The reduction in mucosal oxygen tension following NO inhibition mirrors the hypoxia seen in hemorrhagic shock.
- Further research into local control mechanisms of gut tissue oxygenation can guide therapies to improve gut oxygenation.