Microcirculation Research Group, Faculty of Medicine, Dentistry and Health, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK.
Br J Anaesth. 2012 Jun;108(6):929-35. doi: 10.1093/bja/aes069. Epub 2012 Apr 16.
Propofol acts as an L-type calcium channel (LTCC) antagonist to decrease peripheral resistance and initiate hypotension. This study investigated LTCC sensitivity/expression in hypertension and the role of LTCCs in exaggerated hypotension to propofol in this situation.
Age-matched 12- to 15-week-old normotensive rats [male Wistar Kyoto (WKY)] and spontaneously hypertensive rats (SHR) were used. Propofol (10 mg kg(-1), 10-50 mg kg(-1) h(-1) i.v.) was administered and the mesenteric microcirculation (<70 µm) observed with fluorescent in vivo microscopy using fluorescein isothiocyanate-conjugated bovine serum albumin (100 mg kg(-1) i.v.). Western blotting was used to measure tissue expression of the α(1C) LTCC subtype. Pressure myography was used to assess isolated mesenteric arterioles (<350 µm) in response to BAYK8644 (0.1 nM-1 µM), a specific LTCC channel agonist.
Propofol dilated isolated arterioles {336.6 µM [mean (sd) change 16.2 (5.8)%]}. However, constriction to BAYK8644 was reduced at this concentration of propofol [EC(50)=8.3 (0.1) log mol(-1)] compared with controls [7.4 (0.1) log mol(-1), P<0.05], suggesting that propofol inhibited LTCCs. The sensitivity of LTCCs increased during hypertension, as in vivo there was a greater increase in mean arterial pressure (MAP) to BAYK8644 [10 µg kg(-1), WKY: 59.5 (9.3)%; SHR: 97.7 (6.3)%, P<0.05] with exaggerated constriction of arterioles [10 µg kg(-1), WKY: 9.1 (2.5)%; SHR: 19.1 (2.6)%, P<0.05]. Propofol also decreased MAP in SHR over time (P<0.05), but remained unchanged in WKY. Using western blotting, expression of α(1C) was greater in SHR compared with WKY (P<0.05).
Propofol acts via LTCC channels, with increased channel expression and sensitivity in genetically hypertensive rats. We suggest that increased sensitivity and expression of LTCCs may be a mechanism for exaggerated hypertension during propofol anaesthesia.
丙泊酚作为 L 型钙通道 (LTCC) 拮抗剂，可降低外周阻力并引发低血压。本研究旨在探讨 LTCC 在高血压中的敏感性/表达情况，以及 LTCC 在这种情况下丙泊酚引起的低血压过度反应中的作用。
使用年龄匹配的 12-15 周龄正常血压大鼠[雄性 Wistar Kyoto (WKY)]和自发性高血压大鼠 (SHR)。给予丙泊酚 (10 mg/kg，10-50 mg/kg/h 静脉输注)，并用荧光体内显微镜观察肠系膜微循环(<70 µm)，荧光素异硫氰酸酯结合牛血清白蛋白 (100 mg/kg 静脉注射)。使用 Western blotting 测量组织中 α(1C) LTCC 亚型的表达。使用压力肌描术测量对 BAYK8644(0.1 nM-1 µM)的离体肠系膜小动脉(<350 µm)反应，BAYK8644 是一种特定的 LTCC 通道激动剂。
丙泊酚扩张了离体小动脉[336.6 µM[平均(标准差)变化 16.2(5.8)%)]]。然而，与对照组相比，在丙泊酚此浓度下，BAYK8644 引起的收缩作用减弱[EC(50)=8.3(0.1) log mol(-1)]，提示丙泊酚抑制了 LTCC。高血压期间 LTCC 的敏感性增加，因为体内 BAYK8644 引起的平均动脉压 (MAP)升高更大[10 µg/kg，WKY：59.5(9.3)%;SHR：97.7(6.3)%, P<0.05]，小动脉收缩幅度更大[10 µg/kg，WKY：9.1(2.5)%;SHR：19.1(2.6)%, P<0.05]。丙泊酚随时间也降低了 SHR 的 MAP(P<0.05)，但在 WKY 中无变化。使用 Western blotting，与 WKY 相比，SHR 中的 α(1C)表达更高(P<0.05)。
丙泊酚通过 LTCC 通道起作用，在遗传性高血压大鼠中，通道表达和敏感性增加。我们认为，LTCC 的敏感性和表达增加可能是丙泊酚麻醉期间高血压过度的机制之一。
