Early experimental hypertension preserves the myocardial microvasculature but aggravates cardiac injury distal to chronic coronary artery obstruction

Victor Hugo Urbieta Caceres, Jing Lin, Xiang Yang Zhu, Frederic D. Favreau, Matthew E. Gibson, John A. Crane, Amir Lerman, Lilach O Lerman

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Coronary artery disease is a leading cause of death. Hypertension (HT) increases the incidence of cardiac events, but its effect on cardiac adaptation to coexisting coronary artery stenosis (CAS) is unclear. We hypothesized that concurrent HT modulates microvascular function in chronic CAS and aggravates microvascular remodeling and myocardial injury. Four groups of pigs (n = 6 each) were studied: normal, CAS, HT, and CAS+HT. CAS and HT were induced by placing local irritant coils in the left circumflex coronary artery and renal artery, respectively. Six weeks later multidetector computerized tomography (CT) was used to assess systolic and diastolic function, microvascular permeability, myocardial perfusion, and responses to adenosine in the "area at risk." Microvascular architecture, inflammation, and fibrosis were then explored in cardiac tissue. Basal myocardial perfusion was similarly decreased in CAS and CAS+HT, but its response to adenosine was significantly more attenuated in CAS. Microvascular permeability in CAS+HT was greater than in CAS and was accompanied by amplified myocardial inflammation, fibrosis, and microvascular remodeling, as well as cardiac systolic and diastolic dysfunction. On the other hand, compared with normal, micro-CT-derived microvascular (20-200 μm) transmural density decreased in CAS but not in HT or CAS+HT. We conclude that the coexistence of early renovascular HT exacerbated myocardial fibrosis and vascular remodeling distal to CAS. These changes were not mediated by loss of myocardial microvessels, which were relatively preserved, but possibly by exacerbated myocardial inflammation and fibrosis. HT modulates cardiac adaptive responses to CAS and bears cardiac functional consequences.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume300
Issue number2
DOIs
StatePublished - Feb 2011

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Coronary Stenosis
Microvessels
Coronary Vessels
Hypertension
Wounds and Injuries
Fibrosis
Capillary Permeability
Inflammation
Adenosine
Perfusion
Tomography
Renovascular Hypertension
Irritants
Renal Artery
Coronary Artery Disease
Cause of Death

Keywords

  • Coronary artery stenosis
  • Microvascular dysfunction
  • Remodeling

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Early experimental hypertension preserves the myocardial microvasculature but aggravates cardiac injury distal to chronic coronary artery obstruction. / Urbieta Caceres, Victor Hugo; Lin, Jing; Zhu, Xiang Yang; Favreau, Frederic D.; Gibson, Matthew E.; Crane, John A.; Lerman, Amir; Lerman, Lilach O.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 300, No. 2, 02.2011.

Research output: Contribution to journalArticle

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AB - Coronary artery disease is a leading cause of death. Hypertension (HT) increases the incidence of cardiac events, but its effect on cardiac adaptation to coexisting coronary artery stenosis (CAS) is unclear. We hypothesized that concurrent HT modulates microvascular function in chronic CAS and aggravates microvascular remodeling and myocardial injury. Four groups of pigs (n = 6 each) were studied: normal, CAS, HT, and CAS+HT. CAS and HT were induced by placing local irritant coils in the left circumflex coronary artery and renal artery, respectively. Six weeks later multidetector computerized tomography (CT) was used to assess systolic and diastolic function, microvascular permeability, myocardial perfusion, and responses to adenosine in the "area at risk." Microvascular architecture, inflammation, and fibrosis were then explored in cardiac tissue. Basal myocardial perfusion was similarly decreased in CAS and CAS+HT, but its response to adenosine was significantly more attenuated in CAS. Microvascular permeability in CAS+HT was greater than in CAS and was accompanied by amplified myocardial inflammation, fibrosis, and microvascular remodeling, as well as cardiac systolic and diastolic dysfunction. On the other hand, compared with normal, micro-CT-derived microvascular (20-200 μm) transmural density decreased in CAS but not in HT or CAS+HT. We conclude that the coexistence of early renovascular HT exacerbated myocardial fibrosis and vascular remodeling distal to CAS. These changes were not mediated by loss of myocardial microvessels, which were relatively preserved, but possibly by exacerbated myocardial inflammation and fibrosis. HT modulates cardiac adaptive responses to CAS and bears cardiac functional consequences.

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