Cardiac kinin level in experimental diabetes mellitus: role of kininases.
Diabetes mellitus impairs the cardiac kallikrein-kinin system 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. With the use of 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-induced diabetic rats. Neither basal nor postischemic coronary BK outflow differed between control and diabetic hearts. Reperfusion after 15 min of 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 an unchanged relative kininase contribution compared with controls. In conclusion, despite reduced cardiac KLK synthesis, STZ-induced 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.
Koch
Matthias
M
Department of Cardiology and Pneumology, University Hospital Benjamin Franklin, Free University of Berlin, Berlin, Germany.
Wendorf
Michael
M
Dendorfer
Andreas
A
Wolfrum
Sebastian
S
Schulze
Karsten
K
Spillmann
Frank
F
Schultheiss
Heinz-Peter
HP
Tschöpe
Carsten
C
D000626:Aminopeptidases / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001920:Bradykinin / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism*; D066298:In Vitro Techniques; D016234:Kallikrein-Kinin System / Q000187:drug effects; D007705:Kinins / Q000378:metabolism*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D015260:Neprilysin / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000502:physiology
D001786:Blood Glucose; D007705:Kinins; D000626:Aminopeptidases; C022750:X-Pro aminopeptidase; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin; D001920:Bradykinin