Role of oxidative stress in remodeling of the myocardial microcirculation in hypertension.
OBJECTIVE
We tested the hypothesis that in early hypertension (HT), increased oxidative stress leads to myocardial microvascular remodeling.


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 microm) 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.
Zhu
Xiang-Yang
XY
Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
Daghini
Elena
E
Chade
Alejandro R
AR
Rodriguez-Porcel
Martin
M
Napoli
Claudio
C
Lerman
Amir
A
Lerman
Lilach O
LO
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001808:Blood Vessels / Q000503:physiopathology; D003326:Coronary Circulation; D004334:Drug Administration Schedule; D005260:Female; D006978:Hypertension, Renovascular / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D008833:Microcirculation; D009205:Myocarditis / Q000209:etiology / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D013552:Swine; D014057:Tomography, X-Ray Computed
D000975:Antioxidants