Role of adenosine in functional hyperemia in skeletal muscle as indicated by pharmacological tools.
The hypothesis that adenosine mediates blood flow increments in contracting skeletal muscle was evaluated by intravital microscopy of the microcirculation in the tenuissimus muscle of anesthetized rabbits. Motor nerve stimulation elicited muscle contractions and frequency-dependent arteriolar dilatation, particularly in terminal arterioles. The pulse duration (0.05 ms) and voltage (1.5-5 V) precluded activation of vasoconstrictor fibers, as also indicated by the lack of effect of phentolamine on resting vascular tone and on the hyperemic response to nerve stimulation. The specific adenosine receptor antagonist, 1,3-dipropyl-8-p-sulfo-phenylxanthine (DPSPX; 10(-5) M), attenuated the hyperemic response to muscle contractions. The adenosine uptake inhibitor dipyridamole (10(-8)-10(-6) M) dose-dependently dilated microvessels, an effect prevented by DPSPX (10(-5) M). Moreover, dipyridamole (10(-7) M) augmented contraction-induced hyperemia. The enhancement by dipyridamole was reversed by DPSPX (10(-5) M). The effects of adenosine uptake inhibitor and antagonist were invariably more marked in terminal than in transverse arterioles, and also more pronounced at higher stimulation frequencies. Motor nerve stimulation failed to induce alterations in vascular diameters when the neuromuscular junction was blocked by pancuronium. Thus, our observations indicate that functional hyperemia after motor nerve-induced contractions of the skeletal muscle was of postjunctional origin. Apparently, activation of adenosine receptors was responsible for a part of the evoked vasodilation.
Persson
M G
MG
Department of Physiology, Karolinska Institutet, Stockholm, Sweden.
Ohlén
A
A
Lindbom
L
L
Hedqvist
P
P
Gustafsson
L E
LE
D000241:Adenosine / Q000502:physiology*; D000287:Administration, Topical; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D004176:Dipyridamole / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006973:Hypertension / Q000503:physiopathology*; D007275:Injections, Intravenous; D008297:Male; D009046:Motor Neurons / Q000502:physiology; D009132:Muscles / Q000098:blood supply / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D010197:Pancuronium / Q000008:administration & dosage / Q000494:pharmacology; D011817:Rabbits; D014970:Xanthines / Q000008:administration & dosage / Q000494:pharmacology
D014970:Xanthines; D004176:Dipyridamole; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; D010197:Pancuronium; D000241:Adenosine