October 18, 2002The FASEB Journal
Vasculoprotective Roles of Neuronal Nitric Oxide Synthase
Why the study?
Does nNOS deficiency or inhibition exacerbate arteriosclerotic vascular lesion formation in animal models of vascular injury?
Population
nNOS gene-deficient (nNOS-KO) mice in a carotid artery ligation model and rats in a balloon injury model
Comparison
nNOS gene deficiency or selective inhibition of… vs Wild-type animals or animals without nNOS…
Design
Preclinical
Authors
Discussion
Loading...
Member takes
Implication
Supports nNOS vasculoprotection in animal vascular injury models; leaves open clinical translation to human arteriosclerosis.
Key Points
- To determine the in vivo vasculoprotective role of neuronal nitric oxide synthase (nNOS) in response to vascular injury and arteriosclerotic lesion formation.
- Assessed neointimal formation and constrictive remodeling following carotid artery ligation in nNOS gene-deficient (nNOS-KO) mice compared to controls.
- Evaluated vascular reactivity to calcium-mobilizing stimuli, tissue cGMP production, and neointima development after selective pharmacological inhibition of nNOS in a rat balloon injury model.
- Genetic deletion of nNOS in mice accelerated neointimal hyperplasia and constrictive vascular remodeling induced by blood flow disruption.
- Selective pharmacological inhibition of nNOS in injured rat arteries suppressed tissue cGMP levels, enhanced vasoconstrictor responses to calcium-mobilizing stimuli, and exacerbated neointimal lesion growth.
- nNOS expression was undetectable in uninjured vessels but was selectively upregulated post-injury within the neointima and medial smooth muscle cells.
Structured PICO
Does nNOS deficiency or inhibition exacerbate arteriosclerotic vascular lesion formation in animal models of vascular injury?
P
Population
nNOS gene-deficient (nNOS-KO) mice in a carotid artery ligation model and rats in a balloon injury model
I
Intervention
nNOS gene deficiency (in mice) or selective inhibition of nNOS activity (in rats)
C
Comparator
Wild-type animals or animals without nNOS inhibition (implied)
O
Outcome
Neointimal formation, vascular remodeling, and vasoconstrictor responsessurrogate
Neuronal nitric oxide synthase (nNOS) plays an important vasculoprotective role in suppressing arteriosclerotic vascular lesion formation in vivo following vascular injury.
Cite This Study
Morishita et al. (2002) studied this question.