Reduction of Cardiac Fibrosis Decreases Systolic Performance Without Affecting Diastolic Function in Hypertensive Rats

Oscar H. Cingolani, Xiao Ping Yang, Yun He Liu, Mirko Villanueva, Nour Eddine Rhaleb, Oscar A. Carretero

Research output: Contribution to journalArticlepeer-review

Abstract

Pressure-overload left ventricular hypertrophy (LVH) is characterized by an increase in myocyte size and fibrosis. However, it is not clear how each of these components affects hypertensive heart disease (HHD). We have shown in 2 different rat models of hypertension that cardiac fibrosis can be reduced with N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), an antifibrotic peptide normally present in mammals. To assess how inhibition of fibrosis affects HHD, spontaneously hypertensive rats (SHR) and normotensive controls (WKY) were treated with Ac-SDKP or vehicle. Cardiac systolic and diastolic function were assessed using in vivo pressure-volume (PV) analysis. Left ventricle passive compliance was also determined ex vivo. We found that in SHR, Ac-SDKP normalized left ventricle total collagen content and interstitial collagen fraction without changing myocyte diameter or left ventricle mass. In WKY, collagen did not change significantly after treatment. Ac-SDKP did not affect left ventricle diastolic function, determined in vivo and ex vivo in SHR and WKY, whereas systolic function was significantly decreased in SHR treated with Ac-SDKP and unchanged in treated WKY. We concluded that in adult SHR, reducing left ventricle collagen deposition with Ac-SDKP does not improve diastolic function, whereas it decreases systolic performance. These findings suggest that total left ventricle collagen reduction per se does not necessarily benefit cardiac function. In HHD, other factors besides collagen quantity, such as myocyte hypertrophy and/or collagen type or cross-link, might be targeted to improve cardiac function.

Original languageEnglish (US)
Pages (from-to)1067-1073
Number of pages7
JournalHypertension
Volume43
Issue number5
DOIs
StatePublished - May 2004
Externally publishedYes

Keywords

  • Hypertension
  • Rats, spontaneously hypertensive

ASJC Scopus subject areas

  • Internal Medicine

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