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Nitric Oxide Contributes to Substance P‐Induced Increases in Lung Rapidly Adapting Receptor Activity in Guinea‐Pigs
Author(s) -
Joad Jesse P.,
Kott Kayleen S.,
Bonham Ann C.
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.635bg.x
Subject(s) - nitric oxide , omega n methylarginine , substance p , nitric oxide synthase , arginine , medicine , stimulation , endocrinology , chemistry , nitroarginine , anesthesia , receptor , amino acid , biochemistry , neuropeptide
1 Substance P induces fluid flux via nitric oxide, and fluid flux stimulates lung rapidly adapting receptors (RARs). We therefore proposed that nitric oxide contributes to substance P‐evoked increases in RAR activity. Since substance P decreases dynamic compliance ( C dyn ), which can stimulate RARs, we also determined whether nitric oxide contributed to substance P‐induced effects on pulmonary function. 2 In anaesthetized guinea‐pigs, the effects of substance P on RAR activity, C dyn , pulmonary resistance ( R L ), and arterial blood pressure were measured before and after i.v. infusion of N G ‐methyl‐ l ‐arginine ( l –NMMA; a nitric oxide synthase inhibitor), or l –NMMA followed by l ‐arginine (a nitric oxide precursor which reverses the effects of l –NMMA). 3 Substance P‐evoked increases in RAR activity were blunted by l –NMMA ( P = 0.006 ) but not by l –NMMA– l ‐arginine ( P = 0.42 ). 4 Substance P‐evoked decreases in C dyn were slightly inhibited by l –NMMA ( P = 0.02 ) and slightly enhanced by l ‐NMM A– l ‐arginine ( P = 0.004 ). However, at the time at which l –NMMA maximally reduced substance P‐induced RAR stimulation (the first 30 s), it did not change substance P‐induced decreases in C dyn . 5 Substance P‐evoked increases in R L were not changed by l –NMMA ( P = 0.10 ) and were enhanced by l ‐NMM A– l ‐arginine ( P = 0.03 ). 6 l –NMMA‐evoked increases in mean arterial blood pressure were reversed by l ‐arginine. Substance P‐evoked decreases in mean arterial blood pressure were not changed by l –NMMA or by l –NMMA– l ‐arginine. 7 We conclude that nitric oxide contributes to substance P‐evoked increases in RAR activity and that the increases are most probably independent of decreases in C dyn .

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