Myocardial expression of rat bradykinin receptors and two tissue kallikrein genes in experimental diabetes.
To characterize the role of the kallikrein-kinin system in diabetic cardiopathy, we studied the effect of streptozotocin (STZ) on the regulation of the myocardial bradykinin (BK) receptors, the B1 and B2 type, and two tissue kallikrein genes, rat kallikrein 1 (rKLK1) and rKLK7, in severely hyperglycemic rats. Experiments were performed in STZ-induced diabetic male Wistar rats (n = 7) and compared to controls (n = 7). After extraction of myocardial total RNA, specific oligonucleotides were used to generate reverse transcription PCR (RT-PCR) products from myocardial rKLK1 and rKLK7 mRNA. Southern blot analyses of these RT-PCR products were hybridized with appropriate gene-specific oligonucleotide probes. Myocardial B1 and B2 receptor expression were analyzed by RNase protection assays using specific probes from the coding region of the receptor genes. Twelve weeks after diabetes induction, the rats were normotensive and hyperglycemic and polyuric. We observed an impairment of the main myocardial kinin-forming enzymes, indicated by a reduction of the expression of both, rKLK1 and rKLK7. At this time the myocardial expression of the B1 receptor was not detectable in either group. Thus, the B1 receptor does not play a regulatory role in either the healthy or in STZ-diabetic heart. In contrast, the B2-receptor expression was detectable but did not differ significantly in either group. The reduced synthesis of myocardial tissue KLK implies a reduced capacity to generate BK in diabetic rats. This reduction is not compensated by elevated BK receptor levels. We suggest that alterations of the KKS may contribute to myocardial dysfunction in diabetes mellitus.
Tschöpe
C
C
Department of Cardiology and Pneumology, University Hospital Benjamin Franklin (UKBF), Free University of Berlin, Germany. tsch@zedat.fu-berlin.de
Walther
T
T
Yu
M
M
Reinecke
A
A
Koch
M
M
Seligmann
C
C
Heringer
S B
SB
Pesquero
J B
JB
Bader
M
M
Schultheiss
H
H
Unger
T
T
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D007610:Kallikreins / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000096:biosynthesis*
D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D007610:Kallikreins