Effects of volatile anesthetics on pulmonary vasoactivity in rats with pulmonary hypertension.

麻醉药对重塑血管的血管活性的影响尚不清楚。本研究旨在探讨麻醉药对野百合碱所致肺动脉高压大鼠肺血管活性的影响。首先，通过电生理研究，明确肺血管平滑肌细胞在肺动脉高压中的特征。用全细胞膜片钳技术比较PH大鼠和对照组大鼠PASM细胞的膜电流。PH大鼠钙激活的K~+电流密度小于对照组，而电压门控性K~+电流的密度不低于对照组。4-AP引起的膜电位去极化在PH组明显大于对照组。因此，我们认为PH的PASM细胞容易引起血管收缩。然后，我们尝试用加压的肺动脉来研究PH的α-肾上腺素能血管收缩作用，但制备难度太大。在加压肠系膜小动脉的初步试验中，发现α激动剂不仅引起血管收缩，而且还引起内皮依赖性的振荡血管运动。由于这种振荡可能在器官的区域控制中提供优势，该研究被扩展到阐明α激动剂诱导的振荡的机制。环氧合酶和一氧化氮合酶途径被联合抑制后，这种振荡并未被取消。钙激活的K^+通道阻断剂完全消除了振荡的剩余成分。被广泛使用的麻醉剂异丙酚，即使在环氧合酶和一氧化氮合酶途径被联合抑制后，也能增强这种振荡。这些结果提示，α激动剂诱发的振荡部分是由EDHF介导的，异丙酚可能增强了EDHF介导的超极化。

Effects of anesthetics on vasoactivity of remodeled vessels are unknown. The purpose of this study was to investigate the effects of anesthetics on vasoactivity of pulmonary arteries from rats with monocrotaline-induced pulmonary hypertension (PH).First, electrophysiological study was performed in order to clarify the characteristics of pulmonary artery smooth muscle (PASM) cells in PH. The membrane currents in the PASM cells from PH and control rats were compared using the whole-cell patch clamp technique. The densities of Ca^<2+>-activated K^+ currents but not voltage-gated K^+ currents in PH rats were smaller than those in control rats. A depolarization of membrane potential induced by 4-AP was greater in PH than in control. Therefore, it is suggested that vasoconstriction is easily evoked in the PASM cells in PH.Then, investigation of α-adrenergic vasoconstriction was tried using pressurized pulmonary arteries in PH, however, the preparation was too difficult. In the preliminary trial with pressurized small mesenteric artery, it was found that α-agonist induced not only vasoconstriction but also endothelium-dependent oscillatory vasomotion. Because this oscillation may provide advantages in the regional control of organs, the study was extended to clarifying the mechanisms of the α-agonist-induced oscillation. The oscillation was not abolished after combined inhibition of the cyclooxygenase and NO synthase pathways. The Ca^<2+>-activated K^+ channels blockers completely abolished the remaining component of oscillation. Propofol, widely used anesthetic, potentiated the oscillation even after the combined inhibition of the cyclooxygenase and NO synthase pathways. These results suggest that theα-agonist-induced oscillation is partly mediated by EDHF, and that propofol may potentiate the EDHF-mediated hyperpolarization.