Integrins mediate mechanical compression-induced endothelium-dependent vasodilation through endothelial nitric oxide pathway.
Bottom Line: 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.It was attenuated by inhibition of NO synthase and by mechanical removal of the endothelium.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.
Affiliation: 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.Show MeSH
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Mentions: We verified the passive diameter change of an arterial segment in response to changes in transmural pressure (Fig. 1) by either intraluminal or extraluminal pressure, as the diameter was dictated by the transmural pressure in this isolated vessel preparation. As expected, the passive changes of peak diameter were essentially identical when transmural pressure was imposed by either cyclic intraluminal or extraluminal pressure (Fig. 1). We also found that the vasodilation induced by either cyclic intraluminal or extraluminal pressure in a precontracted vessel segment was determined by the transmural pressure (Fig. 2 A). As shown in Fig. 2 A, the diameter of coronary or skeletal muscle arterial segment decreased via contractile response to endothelin-1 (10−7 mol/L). After the diameter of contractile vessel reached a stable value, the cyclic intraluminal pressure (∼90 to 0 mmHg) was applied during a constant extraluminal pressure (0 mmHg) to generate cyclic transmural pressure. The diameter shows an oscillatory change during the cyclic transmural pressure, which significantly increased over time; i.e., the vessel vasodilated. When the transmural pressure remained constant at 100 mmHg (no pulsatility), the diameter gradually decreased toward the level before the cyclic transmural pressure was applied, i.e., vasoconstriction. While the cyclic extraluminal pressure (0 to ∼90 mmHg) was then applied during a constant intraluminal pressure (∼90 mmHg) to generate cyclic transmural pressure, the diameter showed an oscillatory change during the cyclic transmural pressure with transient vasodilation. The two ways to generate cyclic transmural pressure, constant extraluminal with cyclic intraluminal pressure or constant intraluminal pressure with cyclic extraluminal pressure, resulted in similar vasodilation (Fig. 2 A). At the end of study, the endothelial function was verified by endothelium-dependent vasodilator BK (10−7 mol/L). In fact, the progressive vasoconstriction during the cessation of cyclic loading underscored its role in vasodilation. We varied the magnitude of the cyclic transmural pressure (Fig. 2 B). We found that the magnitude of transmural pressure must be ∼86.3 ± 11.6 mmHg (n = 3) to induce the vasodilation. The in vivo magnitude of pulse pressure caused by cardiac systole and diastole is below the threshold to induce the vasodilation. We also found that the frequency of the cyclic transmural pressure from 0.5 to 1.5 did not change the vasodilation.
Affiliation: 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.