Hyperosmolar Solution Effects in Guinea Pig Airways. I. Mechanical Responses to Relative Changes in Osmolarity

Abstract

In the guinea pig isolated perfused trachea contracted with serosal methacholine (MCh), increasing the osmolarity of the mucosal bathing solution elicits relaxation of smooth muscle mediated by epithelium-derived relaxing factor (EpDRF). The present study was undertaken to determine whether a specific modality of the hyperosmolar stimulus induced the relaxation response. Mucosal hyperosmolar challenge with D-mannitol, N-methyl-D-glucamine (NMDG)-chloride, NMDG-gluconate (NMDG-Glu), or urea elicited relaxation with equal potency. In contrast, hyperosmolar solutions at the serosal surface induced diverse, osmolyte-specific responses. In tracheae contracted with MCh, abrupt replacement of the mucosal modified KrebsHenseleit solution (MKHS) with isosmolar osmolyte solutions to stimulate cell shrinkage elicited five discrete response patterns related to the membrane permeance of the solute, but increasing the osmolarity of the isosmolar solution via the further addition of the same solute always induced relaxation. Similarly, perfusion of the lumen with water induced a transient contraction, but subsequent addition of MKHS, or isosmolar D-mannitol, urea, NMDG-Glu, NaCl, or KCl induced relaxation. Subsequent hyperosmolar addition of the same osmolyteevoked relaxation. Compatible osmolytes had no effect on smooth muscle tone and did not affect responses to hyperosmolar challenge. The results suggest that the airway epithelium acts as an osmolarity sensor, which communicates with airway smooth muscle through EpDRF. The mechanical responses of the smooth muscle resulting from changes in the osmotic environment are associated with discrete modalities of the osmolar stimulus, including membrane reflection of the particles, incremental change in osmolarity and directionality, but not cell shrinkage.

Hyperosmolar Solution Effects in Guinea Pig Airways. III. Studies on the Identity of Epithelium-Derived Relaxing Factor in Isolated Perfused Trachea Using Pharmacological Agents

“…Application of hyperosmolar solution to airway epithelium results in cell shrinkage (for review, see Fedan et al, 2003). Cell volume changes and the resulting compensatory changes in ion transport activity (Rehn et al, 1998) involve the cellular cytoskeleton (Lang et al, 1998).…”

Hyperosmolar Solution Effects in Guinea Pig Airways. IV. Lipopolysaccharide-Induced Alterations in Airway Reactivity and Epithelial Bioelectric Responses to Methacholine and Hyperosmolarity

“…and sacrificed by thoracotomy and bleeding before removing the trachea. Other details of animal use have been given (Fedan et al, 2003a).…”

“…This preparation permits separate application of agents to the mucosal (intraluminal) or serosal (extraluminal) surfaces of the trachea. The method has been described previously (Fedan and Frazer, 1992;Fedan et al, 2003a), along with modifications (Dortch-Carnes et al, 1999) for measuring V t simultaneously with smooth muscle contractile and relaxant responses.…”

“…One such inhibitory substance that has been shown to modulate airway reactivity is the non-nitric oxide nonprostanoid epithelium-derived relaxing factor (EpDRF), which is released in response to hy-perosmolarity 1 at the mucosal or serosal surface of airway epithelial cells (Munakata et al, 1988(Munakata et al, , 1990Fedan et al, 1999Fedan et al, , 2003a. EpDRF release during hyperosmolar challenge occurs in response to the incremental increase in osmolarity (Fedan et al, 2003a) and is associated with epithelial bioelectric events (Dortch-Carnes et al, 1999;Wu et al, 2003). Evidence has been obtained to suggest that hyperosmolar challenge of the epithelium releases carbon monoxide (Fedan et al, 2003b).…”

Hyperosmolarity-Induced Dilation and Epithelial Bioelectric Responses of Guinea Pig Trachea in Vitro: Role of Kinase Signaling

“…The EpDRF-mediated relaxation is not linked to cell shrinkage (Fedan et al, 2004a(Fedan et al, , 2007a. Many cells, but not airway epithelial cells, undergo a compensatory regulatory volume increase (RVI) in the presence of raised osmolarity, resulting from activation of the Na ϩ ,K ϩ ,2Cl Ϫ cotransporter and other ion transport systems, causing an uptake of Na ϩ , Cl Ϫ , and water to restore cell volume.…”