title: L-citrulline reverses the inhibition of nonadrenergic, noncholinergic relaxations produced by nitric oxide synthase inhibitors in guinea pig trachea and human bronchus.
abstract: Nonadrenergic, noncholinergic relaxations were elicited by field stimulation (8 Hz, 1 msec, 12 V for 15 sec) of guinea pig trachea desensitized with capsaicin (1 microM), pretreated with atropine (1 microM), propranolol (1 microM), indomethacin (3 microM) and alpha-chymotrypsin (2 U/ml) and contracted with 3 microM histamine. These relaxations averaged 60 to 80% of the contractions to histamine. The relaxations were inhibited markedly by the addition of the nitric oxide (NO) synthase inhibitor L-nitro-n-arginine (L-NNA)(30 microM), suggesting that these relaxations are due to the release of NO. The inhibition produced by L-NNA was reversed by either L-arginine or L-citrulline. L-Citrulline was both more potent and efficacious than L-arginine in this regard. The ability of L-citrulline to reverse the inhibition produced by L-NNA was not altered by L-glutamine (1 mM). The addition of L-citrulline (1 mM) added before L-NNA was without effect on the relaxant responses to field stimulation but was able to prevent the inhibition produced by L-NNA. L-Citrulline also reversed the inhibition produced by another NO synthase inhibitor, L-nitro monomethyl arginine. Relaxations to field stimulation (16 Hz, 1 msec, 12 V for 15 sec) of human bronchus also were inhibited by 30 microM L-NNA and, as in the guinea pig, this inhibition by L-NNA could be reversed by L-citrulline. These results suggest that L-citrulline is able to overcome the inhibition of NO synthase by NO synthase inhibitors in the guinea pig trachea and human bronchus.
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland.
authors.forename: J L
authors.initials: JL
authors.lastname: Ellis
authors.forename: N
authors.initials: N
authors.lastname: Conanan
mesh_terms: D000328:Adult; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D002956:Citrulline / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D014132:Trachea / Q000187:drug effects* / Q000294:innervation / Q000502:physiology
chemical_list: D019335:Nitroarginine; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases