title: Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension.
abstract: Advanced hypertension (HT), associated with left ventricular hypertrophy (LVH), impairs myocardial microvascular function and structure and leads to increased myocardial hypoxia and growth factor activation. However, the effect of HT on microvascular architecture and its relation to microvascular function, before the development of LVH (early HT), remains unclear. By way of method, pigs were studied after 12 wk of renovascular HT (n = 7) or control (n = 7) animals. Myocardial microvascular function (blood volume and blood flow at baseline and in response to adenosine) was assessed by using electron beam computed tomography (CT). Microvascular architecture was subsequently studied ex vivo using micro-CT, and microvessels (diameter, <500 microm) were counted in situ in three-dimensional images (40-microm on-a-side cubic voxels). Myocardial expression of vascular endothelial growth factor, basic fibroblast growth factor, and hypoxia-inducible factor-1alpha were also measured. By way of results, left ventricular muscle mass was similar between the groups. The blood volume response to intravenous adenosine was attenuated in HT animals compared with normal animals (+7.4 +/- 17.0 vs. +46.2 +/- 12.3% compared with baseline, P = 0.48 and P = 0.01, respectively). Microvascular spatial density in HT animals was significantly elevated compared with normal animals (246 +/- 26 vs. 125 +/- 20 vessels/cm2, P < 0.05) and correlated inversely with the blood volume response to adenosine. Growth factors expression was increased in HT animals compared with control animals. In conclusion, early HT elicits changes in myocardial microvascular architecture, which are associated with microvascular dysfunction and precede changes in muscle mass. These observations underscore the direct and early effects of HT on the myocardial vasculature.
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Disease, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, Minnesota 55905, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Rodriguez-Porcel
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Zhu
authors.forename: Alejandro R
authors.initials: AR
authors.lastname: Chade
authors.forename: Beatriz
authors.initials: B
authors.lastname: Amores-Arriaga
authors.forename: Noel M
authors.initials: NM
authors.lastname: Caplice
authors.forename: Erik L
authors.initials: EL
authors.lastname: Ritman
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006133:Growth Substances / Q000378:metabolism*; D006973:Hypertension / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D008833:Microcirculation / Q000473:pathology* / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D020127:Recovery of Function; D013552:Swine; D020257:Ventricular Remodeling
chemical_list: D006133:Growth Substances