Expressions of bradykinin B2-receptor, kallikrein and kininogen mRNAs in the heart are altered in pressure-overload cardiac hypertrophy in mice.
Angiotensin-converting enzyme inhibitors prevent cardiac hypertrophy in vivo, and a component of this ameliorative effect has been attributed to accumulation of kinins in cardiac tissues. However, little is known regarding the levels of kallikrein-kinin components in the heart during the development of cardiac hypertrophy. The objectives of the present study were to define the effects of pressure-overload cardiac hypertrophy on cardiac levels of kininogen, kallikrein and bradykinin B2 receptor mRNAs. The pressure-overload induced by aortic constriction produced cardiac hypertrophy in mice after 14 and 28d, assessed from the increased ratios of heart weight to body weight and elevation of brain natriuretic peptide mRNA in the heart. B2 receptor mRNA rapidly decreased in the heart within 7 d after the operation, subsequently returning to those of sham-operated animals. In contrast, levels of both low-molecular-weight kininogen and tissue kallikrein mRNAs were increased 7, 14 and 28 d after aortic constriction. These findings suggest that the mechanical load or stretch in cardiac tissue by pressue-overload rapidly produces the downregulation of B2 receptor expression during the initial stage which may allow the promotion of cardiac hypertrophy induced by a mediation of hypertophic factors such as angiotensin II, while upregulation of kininogen and kallikrein mRNAs during the chronic stage may lead to an enhancement of local kinin generation in the heart, from which further progression of cardiac hypertrophy during later stages may be regulated.
Yayama
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakulin University, Japan.
Hiyoshi
H
H
Okamoto
H
H
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D006332:Cardiomegaly / Q000235:genetics*; D017931:DNA Primers; D007610:Kallikreins / Q000235:genetics*; D007704:Kininogens / Q000235:genetics*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000378:metabolism*; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000235:genetics*; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics*
D017931:DNA Primers; D007704:Kininogens; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D007610:Kallikreins