Welsh D G, Segal S S
John B. Pierce Laboratory, Yale University School of Medicine, New Haven, Connecticut 06519, USA.
Am J Physiol. 1997 Jul;273(1 Pt 2):H156-63. doi: 10.1152/ajpheart.1997.273.1.H156.
Acetylcholine (ACh) released at the neuromuscular junction (NMJ) triggers muscle fiber contraction. We tested whether this source of ACh also triggers vasodilation. Arterioles [diameter: 4th order (4A), 18 +/- 3 microns; 2nd order (2A), 35 +/- 2 microns] and feed arteries (60 +/- 4 microns) were observed in retractor muscle of anesthetized hamsters. During stimulation [25% duty cycle (500-ms train, 1 per 2 s) at approximately 40% of maximum isometric tension], a nicotinic receptor antagonist (tubocurarine, 10 microM) prevented contraction, yet 2A and 4A arterioles and feed arteries rapidly (< or = 5 s) dilated (by 9 +/- 2, 11 +/- 3, and 8 +/- 1 microns, respectively; P < 0.05); neither cholinergic innervation of the vasculature nor ACh release from endothelium was apparent. Vasodilator responses doubled (P < 0.05) with cholinesterase inhibition (eserine, 1 microM) and were abolished with muscarinic receptor antagonism (atropine, 10 microM). Microiontophoresis of ACh onto arterioles triggered vasodilation that conducted into feed arteries, confirming functional continuity between intramuscular and extraparenchymal resistance vessels. To determine whether ACh served as a vasodilator during exercise, vascular responses to muscle contraction were measured 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, arteriolar dilation was unaffected by atropine, yet feed artery dilation was attenuated by 60%; this was accompanied by a 50% reduction in functional hyperemia. Our findings indicate that ACh "spillover" from NMJs can coactivate muscarinic receptors, giving rise to a dilation that is conducted into feed arteries. This ascending vasodilation is integral to the full expression of functional hyperemia.
在神经肌肉接头（NMJ）释放的乙酰胆碱（ACh）可触发肌纤维收缩。我们测试了这种ACh来源是否也能触发血管舒张。在麻醉的仓鼠的牵开肌中观察小动脉[直径：四级（4A），18±3微米；二级（2A），35±2微米]和供血动脉（60±4微米）。在刺激期间[以约最大等长张力的40%进行25%占空比（500毫秒串刺激，每2秒1次）]，一种烟碱受体拮抗剂（筒箭毒碱，10微摩尔）可防止收缩，但2A和4A小动脉以及供血动脉迅速（≤5秒）扩张（分别扩张9±2、11±3和8±1微米；P<0.05）；血管的胆碱能神经支配和内皮释放的ACh均不明显。用胆碱酯酶抑制剂（毒扁豆碱，1微摩尔）时血管舒张反应加倍（P<0.05），而用毒蕈碱受体拮抗剂（阿托品，10微摩尔）时反应消失。将ACh微离子导入小动脉可触发血管舒张，并传导至供血动脉，证实了肌内和实质外阻力血管之间的功能连续性。为了确定运动期间ACh是否作为血管舒张剂，在有或没有阿托品的情况下测量了对肌肉收缩的血管反应。在2.5%占空比（50毫秒，每2秒1次）时，阿托品使2A小动脉的血管舒张减弱35%，4A小动脉减弱51%，供血动脉减弱65%。在25%占空比时，小动脉扩张不受阿托品影响，但供血动脉扩张减弱60%；同时功能性充血减少50%。我们的研究结果表明，来自神经肌肉接头的ACh“溢出”可共同激活毒蕈碱受体，引起传导至供血动脉的血管舒张。这种上行性血管舒张是功能性充血充分表达所必需的。
