Mechanism for substance P-induced relaxation of precontracted airway smooth muscle during development

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 276; no. 1; pp. 51 - L56
• Main Authors: Mhanna, Maroun J, Dreshaj, Ismail A, Haxhiu, Musa A, Martin, Richard J
• Format: Journal Article
• Language: English
• Published: United States 01.01.1999
• Subjects: Aging - physiology; Animals; Animals, Newborn; Cyclooxygenase Inhibitors - pharmacology; Dinoprostone - pharmacology; Drug Synergism; Enzyme Inhibitors - pharmacology; In Vitro Techniques; Indomethacin - pharmacology; Muscle Development; Muscle Relaxation - drug effects; Muscle Relaxation - physiology; Muscle, Smooth - drug effects; Muscle, Smooth - growth & development; Muscle, Smooth - physiology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - pharmacology; Rats; Rats, Sprague-Dawley; Substance P - pharmacology; Trachea - drug effects; Trachea - growth & development; Trachea - physiology
• ISSN: 1040-0605; 0002-9513; 1522-1504
• DOI: 10.1152/ajplung.1999.276.1.l51

Departments of 1  Pediatrics and 2  Medicine, Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 Release of substance P (SP) from sensory nerve endings of the tracheobronchial system modulates airway smooth muscle contraction and may cause relaxation of precontracted airways. We sought to elucidate the effect of postnatal maturation on SP-induced relaxation of precontracted airways and determine the roles of endogenously generated nitric oxide (NO) and prostaglandins (PGs). Cylindrical airway segments were isolated from the midtrachea of rats at four different ages, 1, 2, and 4 wk and 3 mo, and contracted to 50-75% of the maximum response induced by bethanechol. SP was then administered in the absence and presence of the NO synthase inhibitor N G -nitro- L -arginine methyl ester ( L -NAME), the PG inhibitor indomethacin, or both. Relaxation of airways with SP decreased significantly with advancing postnatal age. SP-induced tracheal relaxation was consistently attenuated by pretreatment with L -NAME, indomethacin, or both. In a different group of animals, L -NAME significantly attenuated the relaxant response of airways to PGE 2 exposure, but indomethacin had no significant effect on the relaxant response to exogenous NO. We conclude that SP induces a relaxant effect on precontracted airway smooth muscle, which decreases with advancing age and is mediated via SP-induced release of NO and/or PG. maturation; neonatal rats; nitric oxide; prostaglandin