Reversal of experimental renovascular hypertension restores coronary microvascular function and architecture

Am J Hypertens. 2011 Apr;24(4):458-65. doi: 10.1038/ajh.2010.259. Epub 2011 Jan 13.

Abstract

Background: Hypertension (HTN) may lead to left ventricular hypertrophy and vascular dysfunction, which are independent factors for adverse cardiovascular outcomes. We hypothesized that decreased blood pressure by percutaneous transluminal renal angioplasty (PTRA) would improve the function and architecture of coronary microvessels, in association with decreased inflammation and fibrosis.

Methods: Three groups of pigs were studied: normal, HTN, and HTN+PTRA. After 6 weeks of renovascular HTN, induced by placing a local-irritant coil in the renal artery, pigs underwent PTRA or sham. Four weeks later multidetector-computed tomography (CT) was used to assess systolic, diastolic, and microvascular function, and responses to adenosine. Microvascular architecture, oxygen sensors, inflammation, and fibrosis were then explored in cardiac tissue.

Results: PTRA successfully decreased blood pressure and left ventricular hypertrophy. Basal fractional vascular volume (FVV) was similar among the groups, but its response to adenosine was significantly attenuated in HTN, whereas microvascular permeability (MP) and response to adenosine were greater than normal. Both were restored by PTRA. These were accompanied by increased myocardial expression of hypoxia-inducible factor (HIF)-1α, inflammation, and microvascular remodeling, including increased density of epicardial microvessels (20-200 µm), as well as cardiac diastolic dysfunction, all of which improved by reversal of HTN. However, PTRA only partially decreased myocardial fibrosis.

Conclusions: Reversal of early renovascular HTN improved coronary microvascular function and architecture and reversed myocardial hypertrophy and diastolic dysfunction, in association with decreased levels of myocardial ischemia and inflammation markers, underscoring the benefits of blood pressure normalization for preservation of cardiovascular function and structure.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angioplasty
  • Animals
  • Capillary Permeability
  • Female
  • Hypertension, Renovascular / physiopathology*
  • Hypertension, Renovascular / therapy
  • Hypertrophy, Left Ventricular / physiopathology
  • Hypertrophy, Left Ventricular / prevention & control
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • Kidney / blood supply
  • Microvessels / pathology
  • Microvessels / physiology*
  • Procollagen-Proline Dioxygenase / biosynthesis
  • Renal Artery Obstruction / physiopathology
  • Swine
  • Von Hippel-Lindau Tumor Suppressor Protein / biosynthesis

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Procollagen-Proline Dioxygenase
  • Von Hippel-Lindau Tumor Suppressor Protein