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Modulation of nitric-oxide synthase by nicotine
B H Tonnessen1, S R Severson, R D Hurt
1Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
The Journal of Pharmacology and Experimental Therapeutics
|October 25, 2000
Summary
Nicotine directly impacts endothelial nitric-oxide synthase (eNOS) activity, influencing nitric oxide production. This finding may explain varied results in studies examining nicotine
Area of Science:
- Biochemistry
- Physiology
- Pharmacology
Background:
- The effects of nicotine on nitric oxide (NO)-mediated arterial relaxation are debated.
- Endothelial nitric-oxide synthase (eNOS) plays a crucial role in NO production.
Purpose of the Study:
- To investigate whether nicotine directly affects the activity of endothelial nitric-oxide synthase (eNOS).
Main Methods:
- Enzyme assays were performed using NOS isolated from canine aortic endothelial cells and recombinant NOS isoforms (eNOS, nNOS, iNOS).
- NOS activity was measured by the conversion of L-arginine to L-citrulline in vitro, with and without varying concentrations of nicotine.
- Cofactor concentrations (NADPH, FAD, tetrahydrobiopterin) were manipulated to assess interactions with nicotine.
Main Results:
- Nicotine (10(-5) M) increased eNOS-mediated citrulline accumulation by 30% in aortic endothelial cells.
- Nicotine demonstrated a dose-dependent increase in citrulline accumulation for recombinant eNOS and neuronal NOS (nNOS), but not inducible NOS (iNOS).
- Nicotine's effect on eNOS activity was modulated by changes in NADPH concentration.
Conclusions:
- Nicotine significantly affects eNOS activity and citrulline accumulation.
- The interaction between nicotine, NOS, and cofactors like NADPH may explain inconsistent findings regarding nicotine's impact on nitric oxide production.