Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension

Martin G Rodriguez-Porcel, Xiang Yang Zhu, Alejandro R. Chade, Beatriz Amores-Arriaga, Noel M. Caplice, Erik L. Ritman, Amir Lerman, Lilach O Lerman

Research output: Contribution to journalArticle

38 Citations (Scopus)

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 μm) were counted in situ in three-dimensional images (40-μm on-a-side cubic voxels). Myocardial expression of vascular endothelial growth factor, basic fibroblast growth factor, and hypoxia-inducible factor-1α 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume290
Issue number3
DOIs
StatePublished - Mar 2006

Fingerprint

Microvessels
Hypertension
Blood Volume
Adenosine
Left Ventricular Hypertrophy
Intercellular Signaling Peptides and Proteins
Hypoxia-Inducible Factor 1
Muscles
Renovascular Hypertension
X Ray Computed Tomography
Three-Dimensional Imaging
Fibroblast Growth Factor 2
Vascular Endothelial Growth Factor A
Swine
Tomography

Keywords

  • Growth factors
  • Imaging
  • Microcirculation
  • Microcomputed tomography

ASJC Scopus subject areas

  • Physiology

Cite this

Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension. / Rodriguez-Porcel, Martin G; Zhu, Xiang Yang; Chade, Alejandro R.; Amores-Arriaga, Beatriz; Caplice, Noel M.; Ritman, Erik L.; Lerman, Amir; Lerman, Lilach O.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 290, No. 3, 03.2006.

Research output: Contribution to journalArticle

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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 μm) were counted in situ in three-dimensional images (40-μm on-a-side cubic voxels). Myocardial expression of vascular endothelial growth factor, basic fibroblast growth factor, and hypoxia-inducible factor-1α 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.",
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