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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1746.)
© 2006 American Heart Association, Inc.

Vascular Biology

Role of Oxidative Stress in Remodeling of the Myocardial Microcirculation in Hypertension

Xiang-Yang Zhu; Elena Daghini; Alejandro R. Chade; Martin Rodriguez-Porcel; Claudio Napoli; Amir Lerman; Lilach O. Lerman

From the Department of Internal Medicine, Divisions of Nephrology and Hypertension (X.-Y.Z., E.D., A.R.C., L.O.L.) and Cardiovascular Diseases (M.R.-P., A.L., L.O.L.), Mayo Clinic, Rochester, Minn; the Research Center of Excellence in Cardiovascular Diseases and Departments of General Pathology and Medicine (C.N.), University of Naples, Italy; and the Evans Department of Medicine and Whitaker Cardiovascular Institute (C.N.), Boston University, Boston, Mass.

Correspondence to Lilach O. Lerman, MD, PhD, Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. E-mail lerman.lilach{at}mayo.edu

Objective— We tested the hypothesis that in early hypertension (HT), increased oxidative stress leads to myocardial microvascular remodeling.

Methods and Results— Pigs were studied after a 12-week observation: normal (n=8), untreated renovascular HT (n=8), or HT+chronic antioxidant supplementation (HT+A, n=6). Left ventricular muscle mass (LVMM) and myocardial blood flow (MBF) reserve were determined using electron beam computer tomography (CT), and the spatial density and tortuousity of myocardial microvessels (<500 µm) was then measured in myocardial samples with micro-CT. Myocardial microvascular morphology, oxidative stress, inflammation, and growth factor expression were determined in vitro. HT and HT+A had similarly increased arterial pressure and LVMM, but only HT showed impaired MBF response to adenosine. Compared with normal, HT had increased spatial density of myocardial microvessels, which was preserved in HT+A (111.8±7.8, 166.3±15.7, and 106.4±6.1 vessels per cm², respectively). HT also showed microvascular wall thickening, increased systemic and tissue oxidative stress, inflammation, and expression of vascular endothelial growth factor and its receptor Flk-1, most of which were attenuated by antioxidants.

Conclusions— Myocardial microvascular remodeling in early HT is accompanied by tissue oxidative stress, inflammation, and altered growth factor expression, and attenuated by antioxidant intervention. This study underscores a role of increased oxidative stress in modulating myocardial microvascular architecture in early HT.

The mechanisms of myocardial microvascular remodeling in early hypertension (HT) were investigated in pigs. Increased myocardial microvascular density in experimental HT was accompanied by tissue oxidative stress, inflammation, and altered growth factor expression, and attenuated by antioxidant intervention. This study underscores a role of increased oxidative stress in modulating myocardial microvascular architecture in early HT.

Key Words: microcirculation • atherosclerosis • hypertension • oxidative stress • inflammation

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