Naslov
Effect of vecuronium on the release of acetylcholine after nerve stimulation - Reply

Autori
Clifford, Phylip S. ; Valić, Zoran ; Naik, Jay S. ; Buckwalter, John B.

Izvornik
Journal of Applied Physiology (8750-7587) 89 (2000), 3; 1250-1250

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pismo, znanstveni

Ključne riječi
skeletal muscle; contraction; vasodilation; neuromuscular block; vecuronium; dog

Sažetak
To the Editor: We thank Dr. van Santen and Dr. Wierda for the opportunity to provide further data to clarify the involvement of acetylcholine receptors in the vascular responses to skeletal muscle contraction. A muscle contraction is initiated when acetylcholine is released from the motor nerve terminal and interacts with a neuromuscular nicotinic acetylcholine receptor on the motor end plate, causing depolarization that is propagated to the muscle fiber. The regulation of transmitter release at neuromuscular junctions is not fully understood and may vary depending on the type of muscle. Blockade of contraction is traditionally achieved by depolarizing blocking agents that may initiate transient muscle fasciculation or nondepolarizing agents, which are the standard clinical drugs employed for muscle relaxation. Vecuronium, a clinically used nondepolarizing agent, was chosen for our study (1) because of its limited cardiovascular side effects. As pointed out by van Santen and Wierda, nondepolarizing blockers do not interact exclusively with postjunctional receptors, and binding to prejunctional receptors could reduce the amount of acetylcholine released at the motor nerve terminals. We acknowledge that our conclusion from that “ acetylcholine spillover from the motor nerve is not responsible for the increase in blood flow in response to muscle contraction” requires the neuromuscular blocker employed to have negligible prejunctional effects. Although we considered making the argument that vecuronium has a low affinity for prejunctional receptors, van Santen and Wierda kindly provided the optimal solution to the problem by suggesting further studies using a-bungarotoxin, which irreversibly binds postjunctional receptors with no detectable prejunctional effects (2). Because of the importance of this finding to an understanding of exercise hyperemia, we performed the proposed studies using the methods described in the original paper. Tetanic muscle contractions were produced by sciatic nerve stimulation in three anesthetized dogs. The hindlimb blood flow responses to a 1-s stimulation of the cut sciatic nerve (30 Hz, 0.1 ms, 103 motor threshold) and a 30-s train of contractions (50% duty cycle) were determined in duplicate. As expected, the train of contractions used to mimic dynamic exercise produced a larger increment in hindlimb blood flow than a 1-sec tetanic contraction (Fig 1, left). Because of the gradual development of neuromuscular blockade after intravenous administration of a-bungarotoxin (0.2 mg/kg), a 1-h interval was allowed before the nerve stimulations were repeated. At that time, mean arterial pressure had increased by an average of 12 mmHg, and baseline blood flow was slightly reduced (Fig. 1). Sciatic nerve stimulation still produced barely visible contractions in one dog, but no contractions were apparent in the other two dogs. Nevertheless, as illustrated in Fig. 1 (right), the increases in blood flow to a 1-s tetanic contraction and a train of contractions were abolished in all three dogs. The new data, presented in Fig. 1, are virtually identical to those presented in Fig. 5 of our original paper (1). The findings strengthen the conclusions from that paper and from Dyke et al. (3) that acetylcholine spillover is not the physiological mechanism underlying contraction-induced vasodilation. Furthermore, because the muscle pump cannot account for the magnitude of increase in blood flow or the time course of the blood flow response observed after a 1-s contraction, our findings suggest that there is rapid release of a vasoactive substance during muscle contraction. Despite more than a century of research and the identification of a plethora of candidates, the identity of this vasoactive substance remains an enigma.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA