HYPOXIA AND SMOOTH-MUSCLE FUNCTION - KEY REGULATORY EVENTS DURING METABOLIC STRESS

Hypoxia rapidly reduces force in many smooth muscles and we review rec ent data that shed light on the mechanisms involved. As many regulated cellular processes are integrated to co-ordinate smooth muscle contra ctility, the processes responsible for decreased force output with alt ered metabolism are also likely to be many, acting in concert, rather than the actions of one altered parameter. Nevertheless the aim of thi s study is to elucidate the hierarchical series of events that contrib ute to reduced smooth muscle force production during altered metabolis m. We conclude that in many phasic smooth muscles the decrease in forc e can be attributed to impaired electro-mechanical coupling whereby th e Ca2+ transient is reduced. A direct effect of hypoxia on the Ca2+ ch annel may be of key importance. In tonic vascular smooth muscles K-ATP channels may also play a role in the integrated functional responses to hypoxia. There are also many examples of force being reduced, in to nically activated preparations, without a fall in steady-state Ca2+ in deed it usually increases. We examine the roles of altered [ATP], pH, myosin phosphorylation, inorganic phosphate and proteolytic activity o n the [Ca2+]-force relationship during hypoxia. We find no defining fo rce-inhibitory role for any one factor acting alone, and suggest that force most probably falls as a result of the combination of myriad fac tors.