Short-Term Biomechanical Adaptation of the Rat Carotid to Acute Hypertension: Contribution of Smooth Muscle P. FRIDEZ, 1 A. MAKINO, 2 H. MIYAZAKI, 2 J.-J. MEISTER, 1 K. HAYASHI, 2 and N. STERGIOPULOS 1 1 Biomedical Engineering Laboratory, Swiss Federal Institute of Technology, Lausanne, Switzerland and 2 Department of Systems and Human Science, Division of Mechanical Science, Graduate School of Engineering Science, Osaka University, Japan (Received 16 February 2000; accepted 29 November 2000) Abstract—The biomechanical adaptation of the arterial wall to hypertension has been studied extensively in recent years; how- ever, the exact biomechanical contribution of vascular smooth muscle cells VSMCs during the adaptation process in conduit vessels is not known. We induced hypertension in 8 wk old Wistar rats by total ligation of the aorta between the two kidneys. Mean blood pressure increased from 922 (meanSE) mm Hg to approximately 150 mm Hg. Rats were sacrificed 2, 4, and 8 d after surgery and the left common carotid artery was excised for analysis. Wall thickness in- creased by 18% in 8 d and the opening angle by 32% in 4 d. The elastic properties were measured under normal VSMC tone i.e., the amount of VSMC tone under normal conditions also called basal VSMC tone or normal resting VSMC tone, under maximally contracted VSMC NE, 5 10 -7 mol/L) and under totally relaxed VSMC conditions papaverine, 10 -4 mol/L). The most pronounced modifications were the changes in elastic properties related to normal VSMC tone. The functional con- traction ratio at 100 mm Hg, defined as the relative contraction under normal conditions normal VSMC tone, increased by 439% 4 d after the induction of hypertension. The total con- traction capacity of the VSMC increased by 38% within 8 d. The changes in normal VSMC tone led to important changes in the mechanical properties of the arterial wall. Under normal VSMC conditions, compliance at mean pressure 148 mm Hg increased by 159% within 8 d, whereas in the absence of VSMC tone, compliance did not increase significantly. We conclude that in conduit vessels, the VSMC, which is the sens- ing and effecting element of the adaptation process, is sub- jected to large-scale changes during the early phase of arterial adaptation to acute hypertension. © 2001 Biomedical Engi- neering Society. DOI: 10.1114/1.1342054 Keywords—Arterial wall, Remodeling, Hypertrophy, Smooth muscle tone, VSMC, Aortic banding, Conduit vessel. INTRODUCTION Elevated blood pressure is associated with geometri- cal, structural, and functional changes in the arterial wall. 8,24 Specific manifestations of wall adaptation in re- sponse to hypertension include wall thickening, vascular smooth muscle cell VSMC hypertrophy, extracellular matrix production, increased viscoelasticity and altered VSMC contractility, and sensitivity to pharmacological stimulation. 2,6,15,17,18 The precise mechanisms controlling wall adaptation in hypertension remain largely unknown. It is, however, generally accepted that circumferential wall tension is the primary mechanical stimulus for wall adaptation. 9,26 Furthermore, in several studies in which hypertension was either Goldblatt 2K-1C 21,26 or in- duced by aortic constriction, 19 the average circumferen- tial wall stress appears to be normalized at the endpoint of vascular adaptation, thus, supporting the argument that wall stress might be the primary biomechanical stimulus for adaptation. It appears that not only the amount of strain and stress but also the temporal characteristics of the mechanical stimulus i.e., time rate of stretch are mechanotransduced, leading to different types of cyto- skeletal protein synthesis by the VSMC. 11,28 In previous investigations, wall adaptation of conduit arteries in response to induced hypertension has been assessed by means of changes in geometry and/or changes in global elastic or structural properties of the arterial wall. The changes in the biomechanical proper- ties of the VSMC in response to acute hypertension, especially those characterizing VSMC tone amplitude, strain dependence, active stress dynamics, sensitivity to agonists are not studied in detail in conduit vessels. Much of the previous work related to the VSMC adap- tation in induced hypertension was performed on micro- circulation, resistance vessels, or cultured VSMC, 7,13 while the adaptation of VSMC in conduit vessels has been largely ignored with the exception of spontaneously hypertensive rats SHR 1,4,10 and a specific study on rat carotid artery by Cox. 3 Cox reported the long term re- modeling of the mechanical properties including VSMC adaptation to hypertension. This lack of attention to the active properties might have been a result of the tacit assumption that VSMC plays a less significant role in Address correspondence to: Nikolaos Stergiopulos, Ph.D., Biomedi- cal Engineering Laboratory, Swiss Federal Institute of Technology, PSE-Ecublens, 1015 Lausanne, Switzerland. Electronic mail: stergiop@dpmail.epfl.ch Annals of Biomedical Engineering, Vol. 29, pp. 26–34, 2001 0090-6964/2001/291/26/9/$15.00 Printed in the USA. All rights reserved. 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