Affiliation:
1. From the South Dakota Health Research Foundation, Cardiovascular Research Institute, Sioux Falls, SD 57105.
Abstract
Background
—ACE inhibitors (ACEIs) and angiotensin II type 1 (AT
1
) receptor blockers are effective in reducing left ventricular mass in hypertension and heart failure. However, the ability of these drugs to reverse excessive myocyte lengthening and transverse growth in heart failure is unknown.
Methods and Results
—
l
-158,809 (an AT
1
blocker; AT
1
), enalapril (an ACEI), and hydralazine (a vasodilator) were administered to spontaneously hypertensive heart failure rats between 6 and 10 months of age (early treatment) and between 18 and 22 months of age (late treatment). After 4 months of treatment, hemodynamics and chamber dimensions were collected before left ventricular myocyte isolation and subsequent analysis of myocyte shape. Each drug reduced systolic blood pressures to normal values. In the early and late studies, the ACEI reduced myocyte volume. Myocyte length was also reduced in the late study. However, the AT
1
was most effective in reversing myocyte dimensions to near-normal values in both studies. Hydralazine was ineffective in reducing cell size but arrested progression of myocyte lengthening in the late study. Changes in myocyte shape reflected alterations in chamber dimensions and wall thickness.
Conclusions
—Reversal of myocyte hypertrophy was produced in hypertensive/heart failure rats with an AT
1
. The ACEI was effective but to a lesser extent. Results indicate that it is possible to significantly reverse myocyte remodeling pharmacologically even if therapy is initiated near the onset of failure. Further work is needed to determine whether similar results can be obtained in humans.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
96 articles.
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