(Hypertension. 1998;31:39.)
© 1998 American Heart Association, Inc.
Scientific Contributions |
Bradykinin Blocks Angiotensin II–Induced Hypertrophy in the Presence of Endothelial Cells
Abstract—Angiotensin-converting enzyme inhibitors block left ventricular hypertrophy in vivo. A component of this effect has been attributed to tissue accumulation of bradykinin. Little is known regarding the effect of bradykinin on cardiomyocytes. The objectives of the present study were to define the effects of bradykinin on isolated ventricular cardiomyocytes (from adult and neonatal rat hearts) and to determine the extent to which bradykinin blocks hypertrophy in vitro. Bradykinin was found to be a hypertrophic agonist, as defined by increased protein synthesis and atrial natriuretic peptide secretion and expression. Bradykinin (10 µmol/L) increased [3H]phenylalanine incorporation by 23±3% in adult and by 36±10% in neonatal cardiomyocytes. Constitutive atrial natriuretic peptide secretion by neonatal myocytes was increased 357±103%. All effects of bradykinin were abolished by the B2-kinin receptor antagonist Hoe 140. These increases were similar in magnitude to those observed with phenylephrine (20 µmol/L) and angiotensin II (1 µmol/L). However, in cardiomyocytes cocultured with endothelial cells, bradykinin did not increase protein synthesis. Angiotensin II increased [3H]phenylalanine incorporation by 24±3% in adult cardiomyocytes in monoculture and by 22±2% in adult rat cardiomyocytes cocultured with endothelial cells. Bradykinin abolished this angiotensin II–induced hypertrophy in myocytes cultured with endothelial cells but not in myocytes studied in the absence of endothelial cells. In conclusion, bradykinin has a direct hypertrophic effect on ventricular myocytes. The presence of endothelial cells is required for the antihypertrophic effects of bradykinin. The results suggest that the increase in local concentration of bradykinin associated with angiotensin-converting enzyme inhibition is an important mechanism by which hypertrophy can be blocked. Manifestation of this mechanism appears to require bradykinin-stimulated release of paracrine factor(s) from endothelial cells, which are also able to block the hypertrophic effects of Ang II.
Key Words: angiotensin-converting enzyme inhibitors • atrial natriuretic peptide • protein synthesis • angiotensin II • bradykinin • phenylephrine
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