Bradykinin B2 receptor antagonist icatibant reduces inhibitory effect of captopril on growth of cultured neonatal rat cardiomyocytes.
OBJECTIVE
To study whether endogenous kinins are negative modulators in the growth of cardiomyocytes and their possible cellular and molecular mechanisms.


METHODS
Cultured neonatal rat cardiomyocytes were used. Intracellular RNA and protein synthesis were measured by [3H]uridine incorporation and [3H]leucine incorporation, respectively. The expression level of proto-oncogene c-myc, c-fos mRNA was observed by Northern blotting.


RESULTS
Exposure of cardiomyocytes to captopril (Cap, 100 mumol.L-1) for 48 h inhibited the rates of [3H]Urd and [3H]Leu incorporations by 25% and 26%, respectively, and for 2 h inhibited c-myc, c-fos mRNA expression by 75% and 55%, respectively. Treatment of angiotensin II (Ang II, 1 mumol.L-1) for 48 h significantly increased the rates of [3H]Urd and [3H]Leu incorporations and for 1 h induced c-myc, c-fos mRNA overexpression, which were reduced by pretreatment with Cap (100 mumol.L-1). Icatibant acetate (Hoe 140, a specific antagonist of bradykinin B2 receptor) 0.1-10 mumol.L-1 blocked the effects of Cap in a concentration-dependent manner.


CONCLUSIONS
Endogenous kinins exhibited a negative modulatory effect on growth of cardiomyoctes via BK B2 receptor.
Lei
B L
BL
Laboratory of Molecular Pharmacology, Hu-nan Medical University, Changsha, China.
Guo
Z G
ZG
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D000831:Animals, Newborn; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002216:Captopril / Q000037:antagonists & inhibitors*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression; D016762:Genes, fos; D016259:Genes, myc; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D012333:RNA, Messenger; C065679:icatibant; D002216:Captopril; D001920:Bradykinin