Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
Department of Biomechanics, Medicine and Rehabilitation of the Locomotor System, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
Free Radic Biol Med. 2018 Feb 1;115:10-17. doi: 10.1016/j.freeradbiomed.2017.11.010. Epub 2017 Nov 11.
Propofol anesthesia is usually accompanied by hypotension. Studies have shown that the hypotensive effects of propofol increase in patients treated with angiotensin-converting enzyme inhibitors (ACEi). Given that both propofol and ACEi affect nitric oxide (NO) signaling, the present study tested the hypothesis that ACEi treatment induces pronounced hypotensive responses to propofol by increasing NO bioavailability. In this study we evaluated 65 patients, divided into three groups: hypertensive patients chronically treated with ACEi (HT-ACEi; n = 21), hypertensive patients treated with other antihypertensive drugs instead of ACEi, such as angiotensin II receptor blockers, β-blockers or diuretics (HT; n = 21) and healthy normotensive subjects (NT; n = 23). Venous blood samples were collected at baseline and after 10min of anesthesia with propofol 2mg/kg administrated intravenously by bolus injection. Hemodynamic parameters were recorded at each blood sample collection. Nitrite levels were determined by using an ozone-based chemiluminescence assay, while NOx (nitrites+nitrates) levels were measured by using the Griess reaction. Additionally, experimental approaches were used to validate our clinical findings. Higher decreases in blood pressure after propofol anesthesia were observed in HT-ACEi group as compared with those found in NT and HT groups. Consistently, rats treated with the ACEi enalapril showed more intense hypotensive responses to propofol. The hypotensive effects of propofol were associated with increased NO production in both clinical and experimental approaches. Enhanced increases in nitrite levels after propofol anesthesia were observed in HT-ACEi patients compared with NT and HT groups. Accordingly, rats treated with enalapril showed increased vascular NO formation after propofol anesthesia compared with rats receiving vehicle. Our data show that ACEi enhance the hypotensive responses to propofol anesthesia and increase nitrite concentrations. These findings suggest that increased NO bioavailability may account for the enhanced hypotensive effects of propofol in ACEi-treated patients.
异丙酚麻醉通常伴随着低血压。研究表明，血管紧张素转换酶抑制剂（ACEi）治疗的患者，异丙酚的降压作用增加。鉴于异丙酚和 ACEi 都影响一氧化氮（NO）信号，本研究通过增加 NO 生物利用度来检验 ACEi 治疗诱导对异丙酚产生明显降压反应的假设。在这项研究中，我们评估了 65 名患者，分为三组：长期接受 ACEi 治疗的高血压患者（HT-ACEi；n = 21）、接受其他降压药物治疗而非 ACEi 的高血压患者，如血管紧张素 II 受体阻滞剂、β受体阻滞剂或利尿剂（HT；n = 21）和健康的正常血压受试者（NT；n = 23）。静脉血样在基线时采集，并在静脉推注异丙酚 2mg/kg 麻醉 10min 后采集。在每次采血时记录血流动力学参数。通过臭氧化学发光测定法测定亚硝酸盐水平，通过格里斯反应测定 NOx（亚硝酸盐+硝酸盐）水平。此外，还采用实验方法验证了我们的临床发现。与 NT 和 HT 组相比，HT-ACEi 组在异丙酚麻醉后血压下降幅度更大。同样，用 ACEi 依那普利治疗的大鼠对异丙酚的降压反应更为剧烈。在临床和实验方法中，异丙酚的降压作用与 NO 生成增加有关。与 NT 和 HT 组相比，HT-ACEi 患者在异丙酚麻醉后亚硝酸盐水平升高更为明显。相应地，用依那普利治疗的大鼠在接受异丙酚麻醉后血管 NO 形成增加，而接受载体的大鼠则没有。我们的数据表明，ACEi 增强了对异丙酚麻醉的降压反应，并增加了亚硝酸盐浓度。这些发现表明，NO 生物利用度的增加可能是 ACEi 治疗患者异丙酚降压作用增强的原因。
