Submitted on August 9, 2002
Accepted on March 6, 2003
Cardiac kinin level in experimental diabetes mellitus. Role of kininases
Matthias Koch1, Michael Wendorf1, Andreas Dendorfer2, Sebastian Wolfrum2, Karsten Schulze1, Frank Spillmann1, Heinz-Peter Schultheiss1, and Carsten Tschoepe1*
1 Department of Cardiology and Pneumology, University Hospital Benjamin Franklin, Free University of Berlin, Berlin, Berlin, Germany
2 Institute of Experimental and Clinical Pharmacology and Toxicology, Medical University of Luebeck, Luebeck, Germany
* To whom correspondence should be addressed. E-mail: ctschoepe{at}yahoo.com.
Diabetes mellitus (DM) impairs the cardiac kallikrein-kinin system (KKS) by reducing cardiac kallikrein (KLK) and kininogen levels, a mechanism that may contribute to the deleterious outcome of cardiac ischemia in this disease. We studied left ventricular (LV) function and bradykinin (BK) coronary outflow in buffer-perfused, isolated working hearts (n=7) of controls and streptozotocin (STZ)-induced diabetic rats before and after global ischemia. Using selective kininase inhibitors, the activities of angiotensin I-converting enzyme, aminopeptidase P, and neutral endopeptidase were determined by analyzing the degradation kinetics of exogenously administered BK during sequential coronary passages.
Basal LV function and coronary flow were impaired in STZ-diabetic rats. Neither basal, nor post-ischemic coronary BK outflow differed between control and diabetic hearts. Reperfusion after 15 min ischemia induced a peak in coronary BK outflow that was of the same extent and duration in both groups. In diabetic hearts total cardiac kininase activity was reduced by 41.4% with unchanged relative kininase contribution compared to controls.
In conclusion, despite reduced cardiac KLK synthesis, STZ-diabetic hearts are able to maintain kinin liberation under basal and ischemic conditions because of a primary impairment or a secondary downregulation of kinin degrading enzymes.
