Carbon dioxide enhances substance P-induced epithelium-dependent bronchial smooth muscle relaxation in Sprague–Dawley rats
Hypocapnia and hypercapnia constrict and relax airway smooth muscle, respectively, through pH- and calcium (Ca2+)-mediated mechanisms. In this study we explore a potential role for the airway epithelium in these responses to carbon dioxide (CO2). Contractile and
relaxant responses of isolated rat bronchial rings were measured under hypocapnic, eucapnic, and hypercapnic conditions. Substance P was added to methacholine precontracted bronchial rings with and without epithelium. The role of Ca2+ was assessed using Ca2+-free solutions
and a Ca2+ channel blocker, nifedipine. The effects of pH were assessed in solutions with HEPES buffer. Hypocapnic challenge increased the organ bath’s pH and increased bronchial smooth muscle resting tension. This effect was abolished with HEPES buffer and partially inhibited
by nifedipine. Hypocapnic conditions suppressed substance P-induced epithelium-dependent relaxation, whereas hypercapnia augmented the response. The epithelial hypocapnic effect was pH dependent, whereas the hypercapnic effect was pH independent. CO2 had no effect on the epithelial
independent smooth muscle agonists methacholine and isoproterenol. In conclusion our data indicate that, in addition to the effects of pH and Ca2+, CO2 affects airway smooth muscle by a pH-independent, epithelium-mediated mechanism. These findings could potentially lead
to new treatments for asthma involving CO2-sensing receptors in the airways.
Keywords: airway smooth muscle; asthma; asthme; calcium channel; canal calcique; carbon dioxide; dioxyde de carbone; epithelium; hypercapnia; hypercapnie; hypocapnia; hypocapnie; muscle lisse bronchique; pH; substance P; épithélium
Document Type: Research Article
Affiliations: 1: Respiratory Research Group, University of Calgary, Calgary, AB, Canada. 2: Smooth Muscle Research Group, University of Calgary, Calgary, AB, Canada
Publication date: 27 July 2011
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