Hypoxic conditioning in blood vessels and smooth muscle tissues: effects on function, mechanisms, and unknowns

Hypoxic preconditioning, the protective effect of brief, intermittent hypoxic or ischemic episodes on subsequent more severe hypoxic episodes, has been known for 30 yr from studies on cardiac muscle. The concept of hypoxic preconditioning has expanded; excitingly, organs beyond the heart, including the brain, liver, and kidney, also benefit. Preconditioning of vascular and visceral smooth muscles has received less attention despite their obvious importance to health. In addition, there has been no attempt to synthesize the literature in this field. Therefore, in addition to overviewing the current understanding of hypoxic conditioning, in the present review, we consider the role of blood vessels in conditioning and explore evidence for conditioning in other smooth muscles. Where possible, we have distinguished effects on myocytes from other cell types in the visceral organs. We found evidence of a pivotal role for blood vessels in conditioning and for conditioning in other smooth muscle, including the bladder, vascular myocytes, and gastrointestinal tract, and a novel response in the uterus of a hypoxic-induced force increase, which helps maintain contractions during labor. To date, however, there are insufficient data to provide a comprehensive or unifying mechanism for smooth muscles or visceral organs and the effects of conditioning on their function. This also means that no firm conclusions can be drawn as to how differences between smooth muscles in metabolic and contractile activity may contribute to conditioning. Therefore, we have suggested what may be general mechanisms of conditioning occurring in all smooth muscles and tabulated tissue-specific mechanistic findings and suggested ideas for further progress.