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Nitric oxide formation from glyceryl trinitrate in the developing guinea-pig hippocampus
A C Crowe1, M E Chang, B E McLaughlin
1Department of Pharmacology and Toxicology, Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada.
Reproduction, Fertility, and Development
|July 14, 2001
Summary
The hippocampus can convert glyceryl trinitrate (GTN) into nitric oxide (NO). This ability is fully developed early in guinea-pig life and is not age-dependent, suggesting therapeutic potential.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Glyceryl trinitrate (GTN) is an organic nitrate vasodilator.
- GTN functions as a prodrug, requiring biotransformation to nitric oxide (NO) for its pharmacological effects.
- Nitric oxide plays crucial roles in various physiological processes within the brain.
Purpose of the Study:
- To investigate if the hippocampus can biotransform GTN to NO under aerobic conditions.
- To determine if this GTN to NO biotransformation in the hippocampus is dependent on postnatal age.
Main Methods:
- Incubation of guinea-pig hippocampal homogenate with GTN under aerobic conditions at 37°C.
- Measurement of time-dependent nitric oxide (NO) formation.
- Comparison of NO formation across different postnatal ages (days 10, 20, and >60).
Main Results:
- Time-dependent formation of NO was observed when GTN was incubated with hippocampal homogenate.
- The magnitude of GTN-derived NO formation was comparable across all studied postnatal ages.
- Hippocampal capacity for NO formation from GTN is established early in postnatal development.
Conclusions:
- The guinea-pig hippocampus possesses a fully developed capacity to biotransform glyceryl trinitrate (GTN) into nitric oxide (NO) early in postnatal life.
- This NO-forming capacity is not significantly altered with age in the studied postnatal period.
- Targeted NO-donor therapies metabolized in the hippocampus could potentially address conditions linked to reduced NO availability.