title: Soluble guanylate cyclase-dependent relaxation is reduced in the adult rat bronchial smooth muscle.
abstract: Cyclic nucleotides are relaxants of the airway smooth muscle, yet most of the available data were obtained in adult animals. The expression and activity of cyclases have been reported to be developmentally regulated in the lung, and little is known about the age-related changes in their bronchial muscle relaxation potential. We evaluated and compared the newborn and adult rat bronchial smooth muscle response to cyclic AMP- and GMP-dependent agonists in isometric mounted bronchial rings. In acetylcholine-precontracted bronchial muscle, the relaxant response to the cAMP agonist forskolin was not age dependent, but the relaxant response to the nitric oxide (NO) donor sodium nitroprusside (SNP) was significantly greater (P<0.01) in the newborn. To further evaluate the cGMP pathway, we stimulated the soluble guanylate cyclase (sGC) with the specific agonists BAY 41-2272 and YC-1. In keeping with the SNP dose-response curves, the sGC agonists significantly relaxed the newborn, but not the adult bronchial muscle. Protein expression of the sGC alpha1- and beta1-subunits were significantly lower (P<0.01) in the adult compared with the newborn bronchial tissue. Consistent with these results, the NO-stimulated sGC activity was significantly greater in the newborn compared with the adult (P<0.01). In conclusion, the bronchial smooth muscle cGMP-, but not cAMP-dependent, relaxant response is developmentally regulated and significantly reduced in the adult rat.
authors.affiliation: Department of Pediatrics, Hospital for Sick Children, 555 Univ. Ave., Toronto, ON, Canada M5G 1X8. jaques.belik@sickkids.ca
authors.forename: Jaques
authors.initials: J
authors.lastname: Belik
authors.forename: Nadine
authors.initials: N
authors.lastname: Hehne
authors.forename: Jingyi
authors.initials: J
authors.lastname: Pan
authors.forename: Soenke
authors.initials: S
authors.lastname: Behrends
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D006152:Cyclic GMP