Mechanopharmacology of Rho-kinase antagonism in airway smooth muscle and potential new therapy for asthma.

Abstract:

:The principle of mechanopharmacology of airway smooth muscle (ASM) is based on the premise that physical agitation, such as pressure oscillation applied to an airway, is able to induce bronchodilation by reducing contractility and softening the cytoskeleton of ASM. Although the underlying mechanism is not entirely clear, there is evidence to suggest that large-amplitude stretches are able to disrupt the actomyosin interaction in the crossbridge cycle and weaken the cytoskeleton in ASM cells. Rho-kinase is known to enhance force generation and strengthen structural integrity of the cytoskeleton during smooth muscle activation and plays a key role in the maintenance of force during prolonged muscle contractions. Synergy in relaxation has been observed when the muscle is subject to oscillatory length change while Rho-kinase is pharmacologically inhibited. In this review, inhibition of Rho-kinase coupled to therapeutic pressure oscillation applied to the airways is explored as a combination treatment for asthma.

journal_name

Pharmacol Res

journal_title

Pharmacological research

authors

Wang L,Chitano P,Seow CY

doi

10.1016/j.phrs.2020.104995

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

104995

eissn

1043-6618

issn

1096-1186

pii

S1043-6618(20)31303-7

journal_volume

159

pub_type

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