Experiments were performed on isolated frog sartorius muscle and in situ dog skeletal muscle to determine whether adenine nucleotides and their degradation products are released during contraction in concentrations capable of producing arteriolar dilation. ATP was not detectable ( < 1 O -8 M ) in the bathing solution of the resting or contracting frog sartorius muscle. Inorganic phosphate (P,) in the muscle bath increased from 9 x lO" 6 ** to 28 X K Hŵ ith 30 minutes of contraction (2 Hz) or with rest. With the dog hindlimb preparation, ATP, ADP, and AMP were not detectable ( < 5 X 1 0~8 M ) in the venous blood collected after 5 minutes of ischemic contraction whereas P t was present at a concentration of 3.7 X ICMM. Arterial blood levels required to elicit detectable vasodilation for ATP, ADP, AMP, and P, were 28.7 X 1(HM, 27.1 X K H M , 31.4 X K H M and 7.2 X IO^M, respectively. The adenosine concentration in dog muscle increased from 0.7 to 1.5 nmole/g with ischemic contraction, and hypoxanthine and inosine increased from 4.5 to 8.5 nmole/g and 2.0 to 5.5 nmole/g, respectively. The adenosine concentration in venous plasma collected from the hindlimb immediately after termination of the ischemic contraction period was 2.2 X 10~7M as compared to 0.4 X 10~7M in control venous and arterial blood samples. Hypoxanthine and inosine concentrations in venous blood increased 22-and 270-fold, respectively, following ischemic contraction. The calculated interstitial fluid adenosine concentration was twice the arterial concentration of adenosine required to elicit maximal arteriolar dilation. These findings suggest that adenosine may play a role in the metabolic regulation of skeletal muscle blood flow, whereas ATP, ADP, AMP, and P, may not.
KEY WORDSautoregulation of blood flow inosine hypoxanthine skeletal muscle ischemia skeletal muscle contraction peripheral resistance reactive hyperemia functional hyperemia purine derivatives in muscle vascular smooth muscle tone dog frog• For a number of years, the adenine nucleotides have been periodically suggested as mediators of the vasodilation associated with an increase in metabolic activity or