Direct action of general anesthetics on vascular smooth muscle and endothelium of systemic resistance arteries in various pathological conditions with impaired endothelial function.

老年、高血压和糖尿病患者在使用挥发性麻醉剂的全身麻醉期间心血管不稳定的风险增加。我们最近发现，在全身阻力动脉中，内皮的存在极大地影响了挥发性麻醉剂对血管反应性的作用（Anesthesiology 2000;92：1426- 40，2001;95：990-8）。由于衰老、高血压和糖尿病都与内皮功能的改变有关，挥发性麻醉剂可能会对这些人群的血管反应性产生不同的影响。本研究旨在探讨老年、高血压和糖尿病患者血管对挥发性麻醉药反应性的可能变化。（7-8周），中年（24-27周）、老年（81-84周）、链脲霉素诱导的糖尿病（24-27周）和自发性高血压（24-27周）大鼠。实验在以下条件下进行： 关于我们 与健康的年轻或中年大鼠相比，高血压、糖尿病和老年大鼠在内皮存在下对交感神经递质去甲肾上腺素的浓度-反应曲线左移。与健康年轻大鼠相比，高血压、糖尿病和老年大鼠对乙酰胆碱的浓度-反应（即内皮依赖性血管舒张）曲线向右移动。异氟烷和七氟烷，在临床浓度，增强亚最大和最大反应去甲肾上腺素在内皮依赖性的方式在健康的年轻和中年大鼠，但不是在高血压，糖尿病和老年大鼠。在去甲肾上腺素的浓度-反应曲线或麻醉剂对去甲肾上腺素的反应在没有endothelial.In肠系膜阻力动脉的高血压，糖尿病和老年大鼠，内皮功能似乎受损，导致增强收缩反应去甲肾上腺素，衰减血管扩张反应乙酰胆碱，并改变血管反应挥发性麻醉剂。异氟烷或七氟烷对去甲肾上腺素收缩反应的增强作用已被证明是由肠系膜小动脉中的内皮介导的，在存在高血压、糖尿病和衰老的情况下受到抑制，这可能导致在异氟烷或七氟烷麻醉期间经常在高血压、糖尿病和老年受试者中观察到的心血管不稳定。少

Geriatric, hypertensive, and diabetic patients are at increased risk for cardiovascular instability during general anesthesia with volatile anesthetics. We have recently shown that in systemic resistance arteries, volatile anesthetic actions on vascular reactivity are greatly influenced by the presence of endothelium (Anesthesiology 2000;92:1426-40,2001;95:990-8). Since aging, hypertension, and diabetes mellitus are all associated with alterations in endothelial function, volatile anesthetics may influence vascular reactivity differently in those populations. This study was designed to investigate possible changes in vascular responsiveness to volatile anesthetics in the presence of aging, hypertension, and diabetes mellitus.Isometric force was recorded in small mesenteric arteries from young (7-8 weeks), middle-aged (24-27 weeks), geriatric (81-84 weeks), streptozotocin-induced diabetic (24-27 weeks), and spontaneously hypertensive (24-27 weeks) rats. The experiments were performed in … More either presence of endothelium or in its absence.The concentration-response curve to norepinephrine, the sympathetic neurotransmitter, in the presence of endothelium was shifted to the left in the hypertensive, diabetic, and geriatric rats compared with healthy young or middle-aged rats. The concentration-response (i.e.endothelium-dependent vasorelaxation) curve to acethylcholine was shifted to the right in the hypertensive, diabetic, and geriatric rats compared with healthy young rats. Isoflurane and sevoflurane, in clinical concentrations, enhanced both submaximal and maximal responses to norepinephrine in an endothelium-dependent manner in healthy young and middle-aged rats, but not in the hypertensive, diabetic, and geriatric rats. No significant differences were observed in the concentration-response curve to norepinephrine or the anesthetic action on norepinephrine response in the absence of endothelium.In mesenteric resistance arteries from the hypertensive, diabetic, and geriatric rats, endothelial function appears to be impaired, leading to enhanced contractile response to norepinephrine, attenuated vasodilator response to acethylcholine, and altered vascular response to volatile anesthetics. The enhancing action of isoflurane or sevoflurane on contractile response to norepinephrine, which has been shown to be mediated by endothelium in small mesenteric arteries, is inhibited in the presence of hypertension, diabetics, and aging, possibly contributing to the cardiovascular instability often observed in the hypertensive, diabetic, and aged subjects during anesthesia with isoflurane or sevoflurane. Less