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

麻醉药对重建血管活性的影响尚不清楚。本研究的目的是探讨麻醉药对大鼠肺高压（PH）肺动脉血管活性的影响。首先，通过电生理研究阐明肺动脉平滑肌（PASM）细胞在PH下的特征。利用全细胞膜片钳技术比较PH和对照大鼠肺动脉平滑肌细胞的膜电流。PH大鼠Ca^<2+>激活的K^+电流密度小于对照大鼠，而电压门控的K^+电流密度不明显。PH条件下4-AP诱导的膜电位去极化作用大于对照。因此，我们认为PH下PASM细胞容易引起血管收缩。我们尝试在PH下用肺动脉加压法研究α-肾上腺素能血管收缩，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-激动剂不仅能引起血管收缩，还能引起内皮依赖性的血管振荡运动。由于这种振荡可能在器官的区域控制中具有优势，因此本研究将扩展到阐明α-激动剂诱导振荡的机制。联合抑制环加氧酶和NO合成酶途径后，振荡未被消除。Ca^<2+>激活的K^+通道阻滞剂完全消除了振荡的剩余成分。异丙酚是一种广泛使用的麻醉剂，即使在环加氧酶和NO合成酶途径联合抑制后，也能增强振荡。这些结果表明α-激动剂诱导的振荡部分是由EDHF介导的，异丙酚可能会增强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.