Endothelial dysfunction limits the antihypertrophic action of bradykinin in rat cardiomyocytes.
We have previously demonstrated that bradykinin blocks hypertrophy of isolated cardiomyocytes: this is dependent on the release of nitric oxide from endothelial cells. In the present study, we investigated the influence of endothelial dysfunction on the antihypertrophic action of bradykinin. Angiotensin II (1 microM) induced a 34 +/- 2% increase in [3H]phenylalanine incorporation (P<0.001), an in vitro marker of hypertrophy, in adult rat cardiomyocytes co-cultured with bovine aortic endothelial cells. This response was blocked by bradykinin (10 microM), but restored by the nitric oxide synthase inhibitor. N(omega)-monomethyl-L-arginine (100 microM). However, the antihypertrophic effect of bradykinin in co-culture was abolished by 24 h pretreatment of endothelial cells with high glucose (25 mM, to mimic hyperglycemia) and attenuated by hydrogen peroxide (100 microM, to mimic oxidative stress). Pretreatment with oxidized low-density lipoprotein (100 microg/ml for 24 h, to mimic hyperlipidemia) was without effect. The hypertrophic response to angiotensin II was not modified by endothelial cell pretreatment. Furthermore, the ability of bradykinin to elevate cGMP (a marker for nitric oxide) in cardiomyocytes co-cultured with endothelial cells was attenuated by pretreatment with either high glucose or hydrogen peroxide. In conclusion, loss of the cardioprotective action of bradykinin against angiotensin II-induced hypertrophy was associated with impaired nitric oxide release from dysfunctional endothelial cells.
Rosenkranz
A C
AC
Howard Florey Institute, The University of Melbourne, Victoria, Australia.
Dusting
G J
GJ
Ritchie
R H
RH
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000804:Angiotensin II; D006152:Cyclic GMP; D001920:Bradykinin