Down-regulation of bradykinin B2-receptor mRNA in the heart in pressure-overload cardiac hypertrophy in the rat.
To determine the potential role of the cardiac kallikrein-kinin system in the development of cardiac hypertrophy, we studied the expression patterns of kallikrein, kininogen, and bradykinin receptor mRNA in the heart by polymerase chain reaction during the development of pressure-overload-induced left ventricular hypertrophy (LVH) in rats. The abdominal aortic constriction produced LVH after 7, 14, and 28 days. Neither mRNA levels for high-molecular-weight (H-) or low-molecular-weight (L-) kininogens and T-kininogen, nor those for tissue kallikreins, changed during LVH. B(2)-receptor mRNA levels in the left ventricles decreased 4 and 7 days after aortic constriction, subsequently returning to the levels in sham-operated animals. B(2)-receptor densities in cardiac membrane preparations obtained 4 days after aortic constriction significantly decreased compared to preparations from sham-operated rats, whereas the receptor affinity was unchanged. Down-regulation of B(2)-receptor mRNA levels was abolished by oral administration of an angiotensin II type 1 ( AT1) receptor antagonist, candesartan, for 4 days after aortic constriction. Both cardiomyocytes and nonmyocytes obtained from neonatal rat hearts expressed B(2)-receptor mRNA in vitro, and the levels were not changed in either cell type by culture with 1 microM angiotensin II (Ang II). However, when a mixture of cardiomyocytes and nonmyocytes was cultured with 1 microM Ang II, B(2)-receptor mRNA levels decreased within 12 hr; this in vitro effect of Ang II was inhibited by the AT1-receptor antagonist losartan. These results indicate that the mechanical load in the myocardium caused by pressure-overload rapidly produces a down-regulation of B(2)-receptor expression during the initial stage of LVH, probably mediated by activating the AT1-receptor.[1]References
- Down-regulation of bradykinin B2-receptor mRNA in the heart in pressure-overload cardiac hypertrophy in the rat. Yayama, K., Matsuoka, S., Nagaoka, M., Shimazu, E., Takano, M., Okamoto, H. Biochem. Pharmacol. (2003) [Pubmed]
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