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进行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，挥发性麻醉剂对血管反应性的作用很大程度上受内皮细胞的影响(麻醉学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，所以在这些人群中，挥发性麻醉药对血管反应性的影响可能是不同的。本研究旨在研究老年(7-8周)、中年(24-27周)、老年(81-84周)、链脲佐菌素诱导的糖尿病(24-27周)和自发性高血压(24-27周)大鼠肠系膜小动脉对挥发性麻醉药的血管反应性的变化。这些实验是在…进行的高血压、糖尿病和老年大鼠与健康的年轻或中年大鼠相比，有内皮存在时对交感神经递质去甲肾上腺素的浓度-反应曲线左移。与健康的年轻大鼠相比，高血压、糖尿病和老年大鼠对乙酰胆碱的浓度-反应(即内皮依赖性血管松弛)曲线右移。临床浓度的异氟醚和七氟醚以内皮依赖的方式增强健康青年和中年大鼠对去甲肾上腺素的次最大和最大反应，但在高血压、糖尿病和老年大鼠中没有。高血压、糖尿病和老年大鼠的肠系膜阻力动脉的内皮功能受损，导致对去甲肾上腺素的收缩反应增强，对乙酰胆碱的血管扩张反应减弱，对挥发性麻醉剂的血管反应改变。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内皮细胞介导的，但在高血压、糖尿病和老年患者存在时，这种增强作用受到抑制，可能是高血压、糖尿病和老年受试者在异氟烷或七氟烷麻醉期间经常观察到的心血管不稳定的原因。较少

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