COACTIVATION OF RESISTANCE VESSELS AND MUSCLE-FIBERS WITH ACETYLCHOLINE-RELEASE FROM MOTOR NERVES

Acetylcholine (ACh) released at the neuromuscular junction (NMJ) trigg ers muscle fiber contraction. We tested whether this source of ACh als o triggers vasodilation. Arterioles [diameter: 4th order (4A), 18 +/- 3 mu m; 2nd order (2A), 35 +/- 2 mu m] and feed arteries (60 +/- 4 mu m) were observed in retractor muscle of anesthetized hamsters. During stimulation [25% duty cycle (500-ms train, 1 per 2 s) at similar to 40 % of maximum isometric tension], a nicotinic receptor antagonist (tubo curarine, 10 mu M) prevented contraction, yet 2A and 4A arterioles and feed arteries rapidly (less than or equal to 5 s) dilated (by 9 +/- 2 , 11 +/- 3, and 8 +/- 1 mu m, respectively; P < 0.05); neither choline rgic innervation of the vasculature nor ACh release from endothelium w as apparent. Vasodilator responses doubled (P < 0.05) with cholinester ase inhibition (eserine, 1 mu M) and were abolished with muscarinic re ceptor antagonism (atropine, 10 mu M). Microiontophoresis of ACh onto arterioles triggered vasodilation that conducted into feed arteries, c onfirming functional continuity between intramuscular and extraparench ymal resistance vessels. To determine whether ACh served as a vasodila tor during exercise, vascular responses to muscle contraction were mea sured in the presence or absence of atropine. With 2.5% duty cycle (50 ms, 1 per 2 s), atropine attenuated vasodilation by 35% in 2A and 51% in 4A arterioles and by 65% in feed arteries. With 25% duty cycle, ar teriolar dilation was unaffected by atropine, yet feed artery dilation was attenuated by 60%; this was accompanied by a 50% reduction in fun ctional hyperemia. Our findings indicate that ACh ''spillover'' from N MJs can coactivate muscarinic receptors, giving rise to a dilation tha t is conducted into feed arteries. This ascending vasodilation is inte gral to the full expression of functional hyperemia.