Ischemic preconditioning - an opiate constitutive nitric oxide molecular hypothesis.
Coronary artery disease is the number one cause of adult mortality due to a medical illness in the United States. Exciting new studies are looking at the role transient ischemia may play in preconditioning the myocardium to reduce the degree of infarction following a sustained ischemic insult. In this speculative review, we surmise ischemic preconditioning and the resulting protection afforded by it in response to abnormal insults arises from an already existing physiological process that may be associated with exercise. A brief ischemic episode mimics the cells response to normal dips in ATP levels caused by metabolic demand. In so doing, via constitutive nitric oxide synthase derived nitric oxide, it temporarily down regulates a cells excitatory state, thus protecting it from the next insult. Within this context, opiate and opioid actions can be incorporated into the protection scenario, as can other signal molecules since they may release nitric oxide. Instead of ischemia inducing nitric oxide release via a drop of ATP levels, various signal molecules, such as opiate alkaloids, have their cell surface receptors coupled to constitutive nitric oxide synthase thereby releasing nitric oxide, initiating associated cell activity dampening action. In conclusion, it appears as though endogenous nitric oxide stimulators offer their selective preconditioning protection by joining an already existing process that limits activation following normal physical exertion.
Stefano
G B
GB
Neuroscience Research Institute, State University of New York College at Old Westbury, Old Westbury, New York 11568, USA. stefanog@surg.som.sunysb.edu
Neenan
K
K
Cadet
P
P
Magazine
H
H
Bilfinger
T V
TV
D000255:Adenosine Triphosphate / Q000378:metabolism; D006801:Humans; D019194:Ischemic Preconditioning; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology*; D018847:Opioid Peptides / Q000502:physiology*
D018847:Opioid Peptides; D009569:Nitric Oxide; D000255:Adenosine Triphosphate