Myocardial Laminar Organization Is Retained in Angiotensin-Converting Enzyme Inhibitor Treated SHRs

Abstract

Background: Cardiac remodeling underpinning progressive hypertensive heart disease alters the three-dimensional structure of the extracellular matrix, as well as the laminar organization of myocardial sheetlets. The effect of pharmacological intervention on microstructural remodeling is not known. Objective: To examine the changes in myocardial microstructure that occur as a result of hypertensive heart disease, and the effect of pharmacological treatment. Methods: The spontaneously hypertensive rat (SHR) model of hypertensive heart disease was studied, and compared with the normotensive Wistar Kyoto (WKY) rat, and SHRs treated with angiotensin converting enzyme inhibitors (TSHR). Cardiac magnetic resonance was used to assess cardiac function and ventricular geometry. Excised myocardium was stained (picrosirius red) for collagen and extended volume confocal microscopy used to produce high-resolution image stacks. Results: At 24 months, TSHRs had significantly greater ejection fraction (P < 0.05), and performed significantly less stroke work than the untreated diseased SHRs (P < 0.01). TSHR hearts displayed no increased collagen deposition between sheetlets at 14 months, unlike SHR hearts at the same age, which showed thick collagen and scarring. Laminar organization was retained in aged TSHR hearts, while it was progressively lost in aged SHR hearts. Conclusions: In aged SHRs, angiotensin converting enzyme inhibition attenuates remodeling of myocardial extracellular matrix, preserves the laminar organization of myocardial sheetlets, and helps to maintain normal cardiac function.