Inhibition by L-N(G)-Nitro-L-arginine of nonadrenergic-noncholinergic- mediated relaxations of human isolated central and peripheral airways

J. L. Ellis, Bradley J Undem

Research output: Contribution to journalArticle

Abstract

Human isolated central (5 to 12 mm) and peripheral (<2 mm) bronchi were contracted with 3 μM histamine. Relaxations were then evoked by electrical field stimulation (EFS) (1 to 32 Hz, 1 ms, 12 V for 15 s in the presence of indomethacin, atropine, and propranolol). The magnitude, time-course, and frequency-response relationship of these nonadrenergic, noncholinergic (NANC) relaxations were similar in the central and the peripheral airways. N(G)- Nitro-L-arginine (L-NOARG) (10 μM) inhibited the tetrodotoxin-sensitive NANC relaxations in both central and peripheral bronchi, whereas the stereoisomer D-NOARG was without effect. This inhibition was reversed by L-arginine (1 mM) but not be D-arginine (1 mM). The nitric oxide donor compound, 3- morpholinosydnonimine (SIN-1), was equipotent at relaxing the central and peripheral airways. Vasoactive intestinal peptide (VIP), although it relaxed central airways, was virtually ineffective in relaxing the peripheral airways. In addition, the peptidase, α-chymotrypsin, at a concentration that blocked relaxations to VIP, was without effect on NANC relaxations in the central bronchi. The results support the following hypotheses: (1) both central and peripheral airways receive nonadrenergic relaxant innervation; (2) the relaxant response to electrical stimulation of this system is dependent on a pathway involving L-arginine; and (3) the relaxant response does not appear to involve VIP, but it may involve the production of nitric oxide.

Original languageEnglish (US)
Pages (from-to)1543-1547
Number of pages5
JournalAmerican Review of Respiratory Disease
Volume146
Issue number6
StatePublished - 1992

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Arginine
Vasoactive Intestinal Peptide
Bronchi
Nitroarginine
Electric Stimulation
Stereoisomerism
Nitric Oxide Donors
Tetrodotoxin
Chymotrypsin
Atropine
Propranolol
Indomethacin
Histamine
Nitric Oxide
Peptide Hydrolases

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

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title = "Inhibition by L-N(G)-Nitro-L-arginine of nonadrenergic-noncholinergic- mediated relaxations of human isolated central and peripheral airways",
abstract = "Human isolated central (5 to 12 mm) and peripheral (<2 mm) bronchi were contracted with 3 μM histamine. Relaxations were then evoked by electrical field stimulation (EFS) (1 to 32 Hz, 1 ms, 12 V for 15 s in the presence of indomethacin, atropine, and propranolol). The magnitude, time-course, and frequency-response relationship of these nonadrenergic, noncholinergic (NANC) relaxations were similar in the central and the peripheral airways. N(G)- Nitro-L-arginine (L-NOARG) (10 μM) inhibited the tetrodotoxin-sensitive NANC relaxations in both central and peripheral bronchi, whereas the stereoisomer D-NOARG was without effect. This inhibition was reversed by L-arginine (1 mM) but not be D-arginine (1 mM). The nitric oxide donor compound, 3- morpholinosydnonimine (SIN-1), was equipotent at relaxing the central and peripheral airways. Vasoactive intestinal peptide (VIP), although it relaxed central airways, was virtually ineffective in relaxing the peripheral airways. In addition, the peptidase, α-chymotrypsin, at a concentration that blocked relaxations to VIP, was without effect on NANC relaxations in the central bronchi. The results support the following hypotheses: (1) both central and peripheral airways receive nonadrenergic relaxant innervation; (2) the relaxant response to electrical stimulation of this system is dependent on a pathway involving L-arginine; and (3) the relaxant response does not appear to involve VIP, but it may involve the production of nitric oxide.",
author = "Ellis, {J. L.} and Undem, {Bradley J}",
year = "1992",
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T1 - Inhibition by L-N(G)-Nitro-L-arginine of nonadrenergic-noncholinergic- mediated relaxations of human isolated central and peripheral airways

AU - Ellis, J. L.

AU - Undem, Bradley J

PY - 1992

Y1 - 1992

N2 - Human isolated central (5 to 12 mm) and peripheral (<2 mm) bronchi were contracted with 3 μM histamine. Relaxations were then evoked by electrical field stimulation (EFS) (1 to 32 Hz, 1 ms, 12 V for 15 s in the presence of indomethacin, atropine, and propranolol). The magnitude, time-course, and frequency-response relationship of these nonadrenergic, noncholinergic (NANC) relaxations were similar in the central and the peripheral airways. N(G)- Nitro-L-arginine (L-NOARG) (10 μM) inhibited the tetrodotoxin-sensitive NANC relaxations in both central and peripheral bronchi, whereas the stereoisomer D-NOARG was without effect. This inhibition was reversed by L-arginine (1 mM) but not be D-arginine (1 mM). The nitric oxide donor compound, 3- morpholinosydnonimine (SIN-1), was equipotent at relaxing the central and peripheral airways. Vasoactive intestinal peptide (VIP), although it relaxed central airways, was virtually ineffective in relaxing the peripheral airways. In addition, the peptidase, α-chymotrypsin, at a concentration that blocked relaxations to VIP, was without effect on NANC relaxations in the central bronchi. The results support the following hypotheses: (1) both central and peripheral airways receive nonadrenergic relaxant innervation; (2) the relaxant response to electrical stimulation of this system is dependent on a pathway involving L-arginine; and (3) the relaxant response does not appear to involve VIP, but it may involve the production of nitric oxide.

AB - Human isolated central (5 to 12 mm) and peripheral (<2 mm) bronchi were contracted with 3 μM histamine. Relaxations were then evoked by electrical field stimulation (EFS) (1 to 32 Hz, 1 ms, 12 V for 15 s in the presence of indomethacin, atropine, and propranolol). The magnitude, time-course, and frequency-response relationship of these nonadrenergic, noncholinergic (NANC) relaxations were similar in the central and the peripheral airways. N(G)- Nitro-L-arginine (L-NOARG) (10 μM) inhibited the tetrodotoxin-sensitive NANC relaxations in both central and peripheral bronchi, whereas the stereoisomer D-NOARG was without effect. This inhibition was reversed by L-arginine (1 mM) but not be D-arginine (1 mM). The nitric oxide donor compound, 3- morpholinosydnonimine (SIN-1), was equipotent at relaxing the central and peripheral airways. Vasoactive intestinal peptide (VIP), although it relaxed central airways, was virtually ineffective in relaxing the peripheral airways. In addition, the peptidase, α-chymotrypsin, at a concentration that blocked relaxations to VIP, was without effect on NANC relaxations in the central bronchi. The results support the following hypotheses: (1) both central and peripheral airways receive nonadrenergic relaxant innervation; (2) the relaxant response to electrical stimulation of this system is dependent on a pathway involving L-arginine; and (3) the relaxant response does not appear to involve VIP, but it may involve the production of nitric oxide.

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