Angiotensin IIaldosterone interaction in human coronary microarteries involves GPR30, EGFR, and endothelial NO synthase
Cardiovascular Research , Volume 94 - Issue 1 p. 136- 143
Aims: The aim of this study was to investigate the aldosteroneangiotensin (Ang) II interaction in human coronary microarteries (HCMAs). Methods and results: HCMAs, obtained from 75 heart-beating organ donors, were mounted in myographs and exposed to Ang II, either directly or following a 30-min pre-incubation with aldosterone, 17β-oestradiol, hydrocortisone, the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, the extracellular regulated kinase 1/2 (ERK1/2) inhibitor PD98059, the GPR30 antagonist G15, or the epidermal growth factor receptor (EGFR) antagonist AG1478. Ang II constricted HCMAs in a concentration-dependent manner. All steroids, at nanomolar levels, potentiated Ang II and G15 prevented this effect. The potentiation disappeared or was reversed into Ang II antagonism at micromolar steroid levels. NO synthase (NOS) inhibition prevented the latter antagonism in the case of 17β-oestradiol, whereas both aldosterone and 17β-oestradiol at micro- (but not nano-) molar levels induced endothelial NOS phosphorylation in human umbilical vein endothelial cells. AG1478, but not SB203580 or PD98059, abolished the Ang II-induced contraction in the presence of aldosterone or 17β-oestradiol, and none of these drugs affected Ang II alone. Conclusion: Steroids including aldosterone affect Ang II-induced vasoconstriction in a biphasic manner. Potentiation occurs at nanomolar steroid levels and depends on GPR30 and EGFR transactivation. At micromolar steroid levels, this potentiation either disappears (aldosterone and hydrocortisone) or is reversed into an inhibition (17β-oestradiol), and this is due to the endothelial NOS activation that occurs at such concentrations. Published on behalf of the European Society of Cardiology. All rights reserved.
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|Organisation||Department of Cardio-Thoracic Surgery|
Batenburg, W.W, Jansen, P.M, van den Bogaerdt, A, & Danser, A.H.J. (2012). Angiotensin IIaldosterone interaction in human coronary microarteries involves GPR30, EGFR, and endothelial NO synthase. Cardiovascular Research, 94(1), 136–143. doi:10.1093/cvr/cvs016