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Am J Physiol Heart Circ Physiol (March 27, 2003). doi:10.1152/ajpheart.00793.2001
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Submitted on September 7, 2001
Accepted on March 20, 2003

CARDIAC INTERSTITIAL BRADYKININ AND MAST CELLS MODULATE THE PATTERN OF LEFT VENTRICULAR REMODELING IN VOLUME OVERLOAD IN THE RAT

Chih-Chang Wei1, Pamela A. Lucchesi2, Jose Tallaj1, Wayne E. Bradley2, Pamela Powell2, and Louis J. Dell'Italia1*

1 Department of Medicine/Cardiovascular Medicine, Birmingham VA Medical Center, Birmingham, AL, USA; Department of Medicine and Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL, USA
2 Department of Medicine and Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL, USA

* To whom correspondence should be addressed. E-mail: dell'italia{at}physiology.uab.edu.

In the current study interstitial fluid (ISF) bradykinin (BK) and angiotensin II (ANG II) levels were measured using cardiac microdialysis in conscious, non-sedated rats at baseline, at 48 hours and 5 days following: sham surgery (Sham, n=6), Sham+ACE inhibitor ramipril (R) (n=6), aorto-caval fistula (ACF) (n=6), and ACF+R (n=6), and ACF+R+BK2 receptor antagonist (HOE140) (n=6). At 5 days both ISF ANG II and BK increased in ACF rats (p<0.05); however, in ACF+R, ISF ANG II did not differ from basal levels and ISF BK increased greater than 3-fold above baseline at 2 and 5 days (p<0.05). Five days after ACF, LV weight/body weight increased 30% (p<0.05) in ACF but did not differ from Sham in ACF+R rats and ACF+R+HOE140, in spite of similar systemic arterial pressures across all ACF groups. However, ACF+R+HOE140 rats had greater post-mortem wall thickness/diameter and smaller cross-sectional diameter compared to ACF+R rats. There was a significant increase in mast cell density in ACF, ACF+R rats that decreased below Sham in ACF+R+HOE140 rats. These results suggest a potentially important interaction of mast cells and BK in the cardiac interstitium that modulates the pattern of LV remodeling in the acute phase of volume overload.




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