Endothelium-Independent Flow-Induced Dilation in the Mouse Carotid Artery

Abstract

Background: We investigated the locus of flow regulation of vascular tone in carotid arteries of C57 Bl/6 and eNOS^–/– mice. Methods: Arterial segments (2–3 mm) were mounted in a perfusion myograph and preconstricted with 1 µM phenylephrine before monitoring flow-induced changes in lumen diameter. Results: Both control and eNOS^–/– mice demonstrated flow-dependent relaxation. This response was not attenuated by the NO synthase antagonist L-NAME, the cyclooxygenase inhibitor indomethacin, the selective guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), the adenylate cyclase inhibitor Rp-8-Br-cAMPs, integrin-binding RGD peptides, or by removal of the endothelium. Hypoxia, a physiological stimulus known to alter endothelium-dependent flow regulation of vascular tone, also failed to attenuate the observed flow-mediated dilation. Conclusions: These findings indicate the existence of a previously unidentified endothelium-independent mechanism of flow-induced dilation in the carotid artery. Further investigations to identify the mechanisms that underlie this response may provide novel therapeutic directions in the treatment of disorders characterized by abnormal flow regulation of vascular tone.

Flow-Dependent Regulation of Krüppel-Like Factor 2 Is Mediated by MicroRNA-92a

“…Carotid arteries were used because the associated flow conditions are well defined 29 and gene expression in these vessels can be manipulated by pluronic gel-based delivery. As shown in Fig.…”

Vascular TRP Channels: Performing Under Pressure and Going with the Flow

“…Shear stress is nearly universally associated with vasodilation in the peripheral vasculature, where research has consistently demonstrated a predominant vasodilatory response to blood flow in conduit arteries, such as femoral (205) and carotid (6,15,16,116,156) arteries, as well as resistance arteries and arterioles, including mesenteric arteries (16,23,98,116,123,188,234), coronary arteries (22,54,78,79,90,91,99,101,105,112,113,133,134,178,203,204,236,237), skeletal muscle feed arteries/arterioles (5-7, 55, 77, 86 -89, 96, 97, 166, 171, 180, 186, 187, 189, 190, 196, 202, 208, 228 -230), and adipose arterioles (153). Interestingly, shear stress is clearly capable of causing vasoconstriction in the cerebral circulation (20, 145,201).…”

cAMP Induces Adhesion of Microvascular Smooth Muscle Cells to Fibronectin via an Epac-Mediated but PKA-independent Mechanism

“…Fibronectin has also been recently shown to upregulate PKG in vascular SMCs as well as in aortic walls [7]. More functional studies also show that integrin engagement and activation induces vasodilation of different blood vessels [44][45][46]. Similarly, activating Epac induces SMC relaxation and vasodilation [47,48].…”