Davies M G, Huynh T T, Hagen P O
Vascular Biology and Atherosclerosis Research Laboratory, Department of Surgery, University of Rochester, New York, USA.
J Surg Res. 2000 Jul;92(1):103-7. doi: 10.1006/jsre.2000.5938.
Dopamine is an endogenous inotropic agent commonly used during coronary artery surgery and in the medical therapy of a revascularized patient. In this study the responses of intimal hyperplastic vein grafts to dopamine are examined.
The in vitro isometric tension responses to dopamine of common carotid jugular vein bypass grafts in New Zealand White rabbits were determined. The responses were compared to those obtained in the jugular vein and in the common carotid artery. Both endothelialized and denuded vessels were precontracted with prostaglandin F(2alpha) and the responses to dopamine were assessed. The contributions of nitric oxide and prostanoids to the response were also determined.
Each vessel showed a biphasic dose response to dopamine with relaxation at low concentrations followed by contraction at high concentrations. Dopamine relaxation in the jugular vein was endothelial independent while in the carotid artery it was endothelial dependent and decreased. The sensitivity of both vessels was significantly greater than the vein graft (6.62 +/- 0.12; P < 0. 05); however, after endothelial denudation, the sensitivity of dopamine-mediated relaxation of the vein graft (8.91 +/- 0.09) was significantly enhanced. Preincubation with L-NMMA (to block NO synthesis) inhibited vein graft relaxation to dopamine and preincubation with indomethacin (to block cyclooxygenase activity) inhibited carotid artery relaxation to dopamine. Addition of phenoxybenzamine, a broad alpha-adrenergic antagonist, enhanced dopamine relaxation in the jugular vein and depressed the relaxation in the carotid artery. There was no effect on the dopamine response in the vein graft. Jugular vein and carotid artery responded to dopamine with cholera toxin-sensitive (Galpha(s)) responses. In contrast, dopamine relaxation in the vein graft was enhanced by inhibition of Galpha(s).
Dopamine relaxation in vein grafts is mediated in part by NO but not by either prostanoids or alpha-adrenergic receptor activation. It is diminished compared to native vessels due to an endothelium-dependent, Galpha(s)-mediated pathway.
多巴胺是一种内源性变力性药物，常用于冠状动脉手术及血管再通患者的药物治疗。本研究检测了内膜增生性静脉移植物对多巴胺的反应。
测定新西兰白兔颈总动脉 - 颈静脉旁路移植物对多巴胺的体外等长张力反应。将这些反应与颈静脉和颈总动脉的反应进行比较。对内皮化和去内皮的血管均先用前列腺素F（2α）进行预收缩，然后评估对多巴胺的反应。还确定了一氧化氮和前列腺素对该反应的作用。
每种血管对多巴胺均呈现双相剂量反应，低浓度时舒张，高浓度时收缩。颈静脉中多巴胺介导的舒张不依赖内皮，而颈动脉中则依赖内皮且减弱。两种血管对多巴胺的敏感性均显著高于静脉移植物（6.62±0.12；P<0.05）；然而，去内皮后，静脉移植物中多巴胺介导的舒张敏感性（8.91±0.09）显著增强。用L - NMMA预孵育（阻断NO合成）可抑制静脉移植物对多巴胺的舒张反应，用吲哚美辛预孵育（阻断环氧化酶活性）可抑制颈动脉对多巴胺的舒张反应。加入酚苄明（一种广泛的α - 肾上腺素能拮抗剂）可增强颈静脉中多巴胺介导的舒张，而抑制颈动脉中的舒张。对静脉移植物的多巴胺反应无影响。颈静脉和颈动脉对多巴胺的反应呈霍乱毒素敏感（Gα(s)）反应。相反，抑制Gα(s)可增强静脉移植物中多巴胺介导的舒张。
静脉移植物中多巴胺介导的舒张部分由NO介导，而非前列腺素或α - 肾上腺素能受体激活。与天然血管相比，由于内皮依赖性、Gα(s)介导的途径，其舒张作用减弱。
