The object of this study was to investigate how changes in the contractile state of smooth muscle would modify oscillatory mechanics of tracheal muscle and lung parenchyma during agonist challenge. Guinea pig tracheal and parenchymal lung strips were suspended in an organ bath. Measurements of length (L) and tension (T) were recorded during sinusoidal oscillations under baseline conditions and after challenge with 1 mM ACh. Measurements were also obtained in strips pretreated with the calmodulin inhibitor calmidazolium (Cmz) or staurosporine (Stauro), a protein kinase C inhibitor. Elastance (E) and resistance (R) were calculated by fitting changes in T, L, and DeltaL/Deltat to the equation of motion. Hysteresivity (eta) was obtained from the following equation: eta = (R/E)2pif, where f is frequency. Finally, maximal unloaded shortening velocity during electrical field stimulation was measured in Cmz-pretreated and control tracheal strips. In tracheal strips, pretreatment with Cmz caused a significant decrease in the eta response to ACh challenge and in maximal unloaded shortening velocity measured during electrical field stimulation; Stauro decreased the T, E, and R response to ACh. In parenchymal strips, Cmz decreased the eta response, whereas Stauro had no effect. These results suggest that modifications in the contractile state of the smooth muscle are reflected in changes in the hysteretic behavior and that T and eta may be controlled independently. Second, inasmuch as changes in eta were similar in parenchymal and tracheal strips, the contractile element is implicated as the structure responsible for constriction-induced changes in the mechanical behavior of the lung periphery.
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http://dx.doi.org/10.1152/jappl.1998.85.1.91 | DOI Listing |
Respir Physiol Neurobiol
July 2024
Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ) - Université Laval, Québec, QC, Canada. Electronic address:
Eight pig tracheal strips were stimulated to contract with log increments of methacholine from 10 to 10 M. For each strip, the concentration-response was repeated four times in a randomized order to measure isometric force, isotonic shortening against a load corresponding to either 5 or 10 % of a reference force, and average force, stiffness, elastance and resistance over one cycle while the strip length was oscillating sinusoidally by 5 % at 0.2 Hz.
View Article and Find Full Text PDFJ Med Chem
February 2024
Department of Medicinal Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
Although β-agonists are crucial for treatment of chronic respiratory diseases, optimizing β-agonistic activity and selectivity remains essential for achieving favorable therapeutic outcomes. A structure-based molecular design workflow was employed to discover a novel class of β agonists featuring a 5-hydroxy-4-benzo[1,4]oxazin-3-one scaffold, which potently stimulated β adrenoceptors (β-ARs). Screening for the β-agonistic activity and selectivity led to the identification of compound (EC = 3.
View Article and Find Full Text PDFRespir Res
April 2023
Department of Mechanical Engineering, University of California at Riverside, Riverside, CA, USA.
Background: Common respiratory illnesses, such as emphysema and chronic obstructive pulmonary disease, are characterized by connective tissue damage and remodeling. Two major fibers govern the mechanics of airway tissue: elastin enables stretch and permits airway recoil, while collagen prevents overextension with stiffer properties. Collagenase and elastase degradation treatments are common avenues for contrasting the role of collagen and elastin in healthy and diseased states; while previous lung studies of collagen and elastin have analyzed parenchymal strips in animal and human specimens, none have focused on the airways to date.
View Article and Find Full Text PDFMol Pharmacol
April 2023
Department of Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, China (J.G., X.W.); Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, Qingdao, China (H.Y., Y.D., Y.L., K.W.); and Institute of Innovative Drugs, Qingdao University, Qingdao, China (Y.L., K.W.)
The uricosuric drug benzbromarone, widely used for treatment of gout, hyperpolarizes the membrane potential of airway smooth muscle cells, but how it works remains unknown. Here we show a novel role of benzbromarone in activation of large conductance calcium-activated K channels. Benzbromarone results in dose-dependent activation of macroscopic big potassium (BK) currents about 1.
View Article and Find Full Text PDFBiomed Res Int
September 2022
Cardiovascular Research Group, Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, 22060 KPK, Pakistan.
Stapf ex Haines () fruit is used traditionally in the treatment of respiratory illnesses including asthma. However, there is no scientific evidence supporting its antiasthmatic activity. The current study was conducted to evaluate its antiasthmatic effects using and approaches.
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