TY - JOUR
T1 - Role of oxidative stress in remodeling of the myocardial microcirculation in hypertension
AU - Zhu, Xiang Yang
AU - Daghini, Elena
AU - Chade, Alejandro R.
AU - Rodriguez-Porcel, Martin
AU - Napoli, Claudio
AU - Lerman, Amir
AU - Lerman, Lilach O.
PY - 2006/8
Y1 - 2006/8
N2 - 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 cm+, 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.
AB - 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 cm+, 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.
KW - Atherosclerosis
KW - Hypertension
KW - Inflammation
KW - Microcirculation
KW - Oxidative stress
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U2 - 10.1161/01.ATV.0000227469.40826.01
DO - 10.1161/01.ATV.0000227469.40826.01
M3 - Article
C2 - 16709946
AN - SCOPUS:33746815796
SN - 1079-5642
VL - 26
SP - 1746
EP - 1752
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 8
ER -