O'Halloran K D, Janssen P L, Bisgard G E
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA.
J Appl Physiol (1985). 1998 Sep;85(3):946-54. doi: 10.1152/jappl.1998.85.3.946.
We examined the ventilatory effects of exogenous dopamine (DA) and norepinephrine (NE) administration in chloralose-anesthetized, paralyzed, artificially ventilated adult goats before and after carotid body denervation (CBD). Intravenous (iv) DA bolus injections and slow iv infusions caused dose-dependent inhibition of phrenic nerve activity (PNA) in carotid body (CB)-intact animals during normoxia and hyperoxia but not during hypercapnia. NE administration in CB-intact goats caused dose-dependent inhibition of PNA of similar magnitude to DA trials. The DA D2-receptor agonists quinelorane and quinpirole inhibited PNA, whereas the DA D1-receptor agonist SKF-81297 had no effect. After CBD, the ventilatory depressant effects of DA persisted, but responses were significantly attenuated compared with CB-intact trials. CBD abolished the inhibitory effect of low-dose NE administration but did not alter ventilatory responses to high-dose NE injection. The peripheral DA D2-receptor antagonist domperidone substantially attenuated the inhibitory effects of DA bolus injections and infusions and reversed the inhibitory ventilatory effect of high-dose DA administration to excitation in some animals. The alpha-adrenoceptor antagonist phentolamine had no effect on DA-induced ventilatory depression. Beta-Adrenoceptor stimulation with isoproterenol produced similar hemodynamic effects to DA administration but had no effect on PNA. We conclude that DA and NE exert both CB-mediated and non-CB-mediated inhibitory effects on respiratory motor output in anesthetized goats. The ventilatory depressant effects that persist in peripherally chemodenervated animals are DA D2-receptor mediated, but their exact location remains speculative.
我们研究了在氯醛糖麻醉、麻痹、人工通气的成年山羊中，在颈动脉体去神经支配（CBD）前后给予外源性多巴胺（DA）和去甲肾上腺素（NE）的通气效应。静脉注射（iv）DA推注和缓慢静脉输注在常氧和高氧期间导致颈动脉体（CB）完整的动物中膈神经活动（PNA）呈剂量依赖性抑制，但在高碳酸血症期间无此作用。在CB完整的山羊中给予NE导致PNA呈剂量依赖性抑制，其幅度与DA试验相似。DA D2受体激动剂喹洛雷和喹吡罗抑制PNA，而DA D1受体激动剂SKF-81297无作用。CBD后，DA的通气抑制作用持续存在，但与CB完整的试验相比，反应明显减弱。CBD消除了低剂量NE给药的抑制作用，但未改变对高剂量NE注射的通气反应。外周DA D2受体拮抗剂多潘立酮显著减弱了DA推注和输注的抑制作用，并在一些动物中使高剂量DA给药的抑制性通气作用逆转为兴奋。α-肾上腺素能受体拮抗剂酚妥拉明对DA诱导的通气抑制无作用。用异丙肾上腺素刺激β-肾上腺素能受体产生的血流动力学效应与给予DA相似，但对PNA无作用。我们得出结论，DA和NE对麻醉山羊的呼吸运动输出发挥CB介导和非CB介导的抑制作用。在外周化学去神经支配的动物中持续存在的通气抑制作用是由DA D2受体介导的，但其确切位置仍具有推测性。
