Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA.
Adv Exp Med Biol. 2010;661:355-73. doi: 10.1007/978-1-60761-500-2_23.
Increases in myofilament Ca2+ sensitivity resulting from stimulation of RhoA and Rho kinase represent a primary mechanism of vasoconstriction and associated pulmonary hypertension resulting from chronic hypoxia (CH). This chapter summarizes recent advances in the understanding of RhoA/Rho kinase signaling mechanisms in pulmonary vascular smooth muscle (VSM) that increase the sensitivity of the contractile apparatus to Ca2+ and contribute to vasoconstriction in this setting. Such advances include the discovery of myogenic tone in small pulmonary arteries from CH rats that contributes to vasoconstriction through a mechanism inherent to the VSM, dependent on Rho kinase-induced Ca2+ sensitization but independent of L-type voltage-gated Ca2+ channels. Additional studies have revealed an important contribution of superoxide anion (O2-)-induced RhoA activation to both receptor-mediated and membrane depolarization-induced myofilament Ca2+ sensitization in hypertensive pulmonary arteries. Xanthine oxidase and NADPH oxidase isoforms are potential sources of O2- that mediate RhoA-dependent vasoconstriction and associated pulmonary hypertension.
肌球蛋白丝 Ca2+敏感性的增加是由 RhoA 和 Rho 激酶的刺激引起的，这代表了慢性缺氧（CH）导致的血管收缩和相关肺动脉高压的主要机制。本章总结了近年来对肺动脉平滑肌（VSM）中 RhoA/Rho 激酶信号转导机制的理解的最新进展，这些机制增加了收缩装置对 Ca2+的敏感性，并有助于在这种情况下的血管收缩。此类进展包括在 CH 大鼠的小肺动脉中发现的肌源性张力，通过固有机制有助于血管收缩，该机制依赖于 Rho 激酶诱导的 Ca2+敏感性，但独立于 L 型电压门控 Ca2+通道。此外的研究揭示了超氧阴离子（O2-）诱导的 RhoA 激活对高血压肺动脉中受体介导的和膜去极化诱导的肌球蛋白丝 Ca2+敏感性增加的重要贡献。黄嘌呤氧化酶和 NADPH 氧化酶同工型是介导 RhoA 依赖性血管收缩和相关肺动脉高压的 O2-的潜在来源。
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