Journal of Cardiac Failure
Volume 12, Issue 6 , Pages 479-486, August 2006

P38 MAP Kinase Activity Is Correlated With Angiotensin II Type 1 Receptor Blocker–Induced Left Ventricular Reverse Remodeling in Spontaneously Hypertensive Heart Failure Rats

  • Qiangrong Liang, MD, PhD
    • ,
  • Andrew C. Elson, BS
    • ,
  • A. Martin Gerdes, PhD

      Affiliations

    • Corresponding Author InformationReprint requests: A. Martin Gerdes, PhD, Cardiovascular Research Institute, South Dakota Health Research Foundation, 1100 East 21st Street, Sioux Falls, SD 57105.

From the University of South Dakota, School of Medicine, Cardiovascular Research Institute-South Dakota Health Research Foundation, Sioux Falls, South Dakota

Received 16 December 2005; received in revised form 22 March 2006; accepted 27 April 2006.

Sioux Falls, South Dakota

Abstract 

Background

Angiotensin II type 1 receptor blocker L-158,809 (ARB) induces reverse left ventricular (LV) remodeling in spontaneously hypertensive heart failure (SHHF) rats. However, the signaling mechanism that mediates ARB-induced reverse LV remodeling remains unclear. The present study was to determine if changes in mitogen-activated protein kinase (MAPK, including ERK, JNK, and p38) signaling correlate with ARB-elicited reversal of cardiac hypertrophy in SHHF rats.

Methods and Results

In 1 set of experiments, 5-month-old lean female SHHF rats were treated with L-158,809 (ARB) or the vasodilator hydralazine (HYD) for 1 month, respectively. In a second set of experiments, 5-month-old SHHF rats were treated with ARB for 6 months or 1 month and then with HYD for 5 months. Either ARB or HYD normalized left ventricular end systolic pressure in SHHF rats relative to normotensive control Wistar Furth (WF) rats at both 6 and 11 months of age, but only ARB reduced heart-to-body weight ratio in SHHF rats to control level. Western blot analysis showed that cardiac p38 MAPK activity was markedly increased in 6-month-old SHHF rats, but dramatically reduced in 11-month-old SHHF rats compared with WF rats, as indicated by the levels of phosphorylated form of p38. The alterations in p38 activity were completely reversed by ARB treatment but not by HYD treatment.

Conclusion

ARB restored normal cardiac p38 activity, which coincided with ARB-induced reverse LV remodeling in SHHF rats, suggesting a strong correlation between p38 signaling and cardiac remodeling.

Key Words: MAP kinase, Hypertension, Cardiac remodeling, Heart failure

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 Supported by grants HL-62459 and P20 RR017662 from the National Institutes of Health, and the South Dakota 2010 Program. The South Dakota Health Research Foundation is a partnership between the Sanford School of Medicine at the University of South Dakota and Sioux Valley Hospital and Health Systems in Sioux Falls. QL is supported by an American Heart Association Scientist Development Grant.

PII: S1071-9164(06)00226-0

doi:10.1016/j.cardfail.2006.04.006

Journal of Cardiac Failure
Volume 12, Issue 6 , Pages 479-486, August 2006

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