Nitric oxide contributes to substance P-induced increases in lung rapidly adapting receptor activity in guinea-pigs.
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 (Cdyn), 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, Cdyn, pulmonary resistance (RL), and arterial blood pressure were measured before and after i.v. infusion of NG-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 Cdyn were slightly inhibited by L-NMMA (P = 0.02) and slightly enhanced by L-NMMA-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 Cdyn. 5. Substance P-evoked increases in RL were not changed by L-NMMA (P = 0.10) and were enhanced by L-NMMA-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 Cdyn.
Joad
J P
JP
Department of Pediatrics, University of California at Davis 95817, USA. jpjoad@ucdavis.edu
Kott
K S
KS
Bonham
A C
AC
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D008168:Lung / Q000098:blood supply / Q000294:innervation* / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012129:Respiratory Function Tests; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*; D013379:Substrate Specificity; D014630:Vagus Nerve / Q000201:enzymology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013373:Substance P; D001120:Arginine; D019001:Nitric Oxide Synthase