Integrins mediate mechanical compression-induced endothelium-dependent vasodilation through endothelial nitric oxide pathway.
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.
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.
Xiao
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Lu
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 gkassab2@calmi2.org.
Ghassan S
GS
Kassab
D000818:Animals; D019245:Compressive Strength / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D016023:Integrins / Q000378:metabolism*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D013552:Swine; D014664:Vasodilation / Q000502:physiology*
D016023:Integrins; D009569:Nitric Oxide