Lu Xiao, Kassab Ghassan S
Department of Biomedical Engineering, Department of Cellular and Integrative Physiology, Department of Surgery, and Indiana Center for Vascular Biology and Medicine, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202.
Department of Biomedical Engineering, Department of Cellular and Integrative Physiology, Department of Surgery, and Indiana Center for Vascular Biology and Medicine, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 Department of Biomedical Engineering, Department of Cellular and Integrative Physiology, Department of Surgery, and Indiana Center for Vascular Biology and Medicine, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 Department of Biomedical Engineering, Department of Cellular and Integrative Physiology, Department of Surgery, and Indiana Center for Vascular Biology and Medicine, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 Department of Biomedical Engineering, Department of Cellular and Integrative Physiology, Department of Surgery, and Indiana Center for Vascular Biology and Medicine, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202
J Gen Physiol. 2015 Sep;146(3):221-32. doi: 10.1085/jgp.201411350.
Cardiac and skeletal muscle contraction lead to compression of intramuscular arterioles, which, in turn, leads to their vasodilation (a process that may enhance blood flow during muscle activity). Although endothelium-derived nitric oxide (NO) has been implicated in compression-induced vasodilation, the mechanism whereby arterial compression elicits NO production is unclear. We cannulated isolated swine (n = 39) myocardial (n = 69) and skeletal muscle (n = 60) arteriole segments and exposed them to cyclic transmural pressure generated by either intraluminal or extraluminal pressure pulses to simulate compression in contracting muscle. We found that the vasodilation elicited by internal or external pressure pulses was equivalent; moreover, vasodilation in response to pressure depended on changes in arteriole diameter. Agonist-induced endothelium-dependent and -independent vasodilation was used to verify endothelial and vascular smooth muscle cell viability. Vasodilation in response to cyclic changes in transmural pressure was smaller than that elicited by pharmacological activation of the NO signaling pathway. It was attenuated by inhibition of NO synthase and by mechanical removal of the endothelium. Stemming from previous observations that endothelial integrin is implicated in vasodilation in response to shear stress, we found that function-blocking integrin α5β1 or αvβ3 antibodies attenuated cyclic compression-induced vasodilation and NOx (NO(-)2 and NO(-)3) production, as did an RGD peptide that competitively inhibits ligand binding to some integrins. We therefore conclude that integrin plays a role in cyclic compression-induced endothelial NO production and thereby in the vasodilation of small arteries during cyclic transmural pressure loading.
心肌和骨骼肌收缩会导致肌内小动脉受压，进而引起小动脉血管舒张（这一过程可能会在肌肉活动期间增强血流）。尽管内皮衍生的一氧化氮（NO）被认为与压迫诱导的血管舒张有关，但动脉压迫引发NO生成的机制尚不清楚。我们将分离的猪（n = 39）心肌（n = 69）和骨骼肌（n = 60）小动脉段插管，并使其暴露于由腔内或腔外压力脉冲产生的周期性跨壁压力下，以模拟收缩肌肉中的压迫。我们发现，由内部或外部压力脉冲引起的血管舒张是等效的；此外，对压力的血管舒张取决于小动脉直径的变化。使用激动剂诱导的内皮依赖性和非依赖性血管舒张来验证内皮细胞和血管平滑肌细胞的活力。对跨壁压力周期性变化的血管舒张小于通过NO信号通路的药理学激活所引起的血管舒张。它通过抑制NO合酶和机械去除内皮而减弱。基于先前的观察结果，即内皮整合素与剪切应力诱导的血管舒张有关，我们发现功能阻断性整合素α5β1或αvβ3抗体可减弱周期性压迫诱导的血管舒张和NOx（NO⁻₂和NO⁻₃）生成，竞争性抑制配体与某些整合素结合的RGD肽也有同样的作用。因此，我们得出结论，整合素在周期性压迫诱导的内皮NO生成中起作用，从而在周期性跨壁压力负荷期间小动脉的血管舒张中起作用。
