Objectives: To determine whether secondhand smoke (SHS)
induces pulmonary artery endothelial dysfunction, and whether dietary
l-arginine supplementation is preventive.
Background: SHS causes coronary and peripheral arterial
Methods: The effects of
l-arginine supplementation (2.25% solution) and SHS (10
weeks) on pulmonary vascular reactivity were examined in 32 rabbits fed
a normal diet. Endothelium-dependent relaxation of precontracted
pulmonary artery segments was studied using acetylcholine and calcium
ionophore. Endothelium-independent relaxation was studied using
nitroglycerin. Endothelial and serum l-arginine levels were
measured by chromatography. In eight SHS-exposed and in eight control
rats, pulmonary artery nitric oxide synthase (NOS) activity and
arginase activity were studied using the titrated arginine to
citrulline conversion assay.
reduced maximal acetylcholine-induced (p = 0.04) and calcium
ionophore-induced (p = 0.02) relaxation. l-Arginine
increased maximal acetylcholine-induced (p = 0.047) vasodilation. SHS
and l-arginine did not influence nitroglycerin-induced
relaxation. SHS reduced endothelial l-arginine (p = 0.04)
but not serum l-arginine. l-Arginine
supplementation increased endothelial (p = 0.007) and serum
l-arginine (p < 0.0005). Endothelium-dependent
relaxation induced by acetylcholine and calcium ionophore varied
directly with endothelial (r = 0.67,
r = 0.67) and serum l-arginine
(r = 0.43, r = 0.45), respectively.
SHS reduced constitutive NOS activity (p = 0.03).
Conclusions: SHS reduces pulmonary artery
endothelium-dependent relaxation by decreasing NOS activity and
possibly by decreasing endothelial arginine content.
l-Arginine supplementation increases serum and endothelial
l-arginine stores and prevents SHS-induced endothelial
dysfunction. l-Arginine may offset the deleterious effect
of SHS on pulmonary arteries by substrate loading of the nitric oxide