Department of Physiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA.
Adv Exp Med Biol. 2010;661:77-96. doi: 10.1007/978-1-60761-500-2_5.
Pulmonary blood pressure is a function of the resistance of the intrapulmonary blood vessels. Consequently, the mechanisms controlling blood vessel smooth muscle cell (SMC) contraction serve as potential sites for hypertension therapy. To explore these mechanisms, access to the intrapulmonary vessels is required and this is provided by the observation of a unique lung slice preparation with microscopy. There are 2 major processes that determine SMC tone; the intracellular Ca(2+) concentration and the sensitivity of the SMCs to Ca(2+). Agonist-induced increases in Ca(2+) occur in the form of propagating Ca(2+) oscillations that predominately utilize internal Ca(2+) stores and inositol trisphosphate receptors. The frequency of these Ca(2+) oscillations correlates with contraction. Agonists also increase Ca(2+) sensitivity of SMCs to enhance contraction. Changes in membrane potential mediated by KCl also stimulate contraction via slow Ca(2+) oscillations and increased sensitivity. However, these slow Ca(2+) oscillations rely on Ca(2+) influx to drive the cyclic release of over-filled Ca(2+) stores via the ryanodine receptor. The relaxation of SMC tone can be induced by the reduction of the frequency of the Ca(2+) oscillations and the Ca(2+) sensitivity by b(2)-adrenergic agonists or nitric oxide.
肺血管血压是肺内血管阻力的功能。因此，控制血管平滑肌细胞（SMC）收缩的机制可作为高血压治疗的潜在靶点。为了探索这些机制，需要获得肺血管的通路，这可以通过显微镜观察一种独特的肺切片制备来实现。有 2 个主要过程决定了 SMC 的张力；细胞内 Ca(2+)浓度和 SMC 对 Ca(2+)的敏感性。激动剂诱导的 Ca(2+)增加以传播 Ca(2+)振荡的形式发生，主要利用内部 Ca(2+)储存库和肌醇三磷酸受体。这些 Ca(2+)振荡的频率与收缩相关。激动剂还增加了 SMC 对 Ca(2+)的敏感性，以增强收缩。KCl 介导的膜电位变化也通过缓慢的 Ca(2+)振荡和增加的敏感性刺激收缩。然而，这些缓慢的 Ca(2+)振荡依赖于 Ca(2+)内流，通过兰尼碱受体驱动过充 Ca(2+)储存库的循环释放。通过β2-肾上腺素能激动剂或一氧化氮，可降低 Ca(2+)振荡的频率和 Ca(2+)敏感性，从而诱导 SMC 张力的松弛。
