High angiotensin II state without cardiac remodeling (Bartter's and Gitelman's syndromes): Are angiotensin II type 2 receptors involved?

Background/aims: While Angiotensin II (Ang II) is a major factor in the development of cardiomyocyte hypertrophy and a pivotal role for Ang II signals via ERK1/2 has been identified, mechanism(s) responsible are still unclear. As Bartter's and Gitelman's syndrome patients (BS/GS) have increased Ang II, and yet normo/hypotension, hyporesponsiveness to pressors and blunted Ang II signaling via type I receptors (AT1R), this study assesses BS/GS's left ventricular (LV) mass and structure as well as Ang II induced ERK1/2 phosphorylation compared with essential hypertensive patients (EH) and normotensive healthy subjects (C) to gain insight into Ang II mediated processes. Methods: Indices of cardiac hypertrophy were determined by M-mode, two-dimensional echo Doppler and ERK phosphorylation by Western blot. Results: None of BS/GS exhibited LV remodelling; LV mass, LV end-diastolic volume and mass/volume ratio were unchanged vs C (60 +/- 14 g/m(2) vs 64 +/- 12, 64 +/- 12 ml/m(2) vs 60 +/- 8 and 0.95 +/- 0.2 vs 1.0 +/- 0.2, respectively) and reduced vs EH (119 +/- 15, p<0.001, 78 +/- 9, p<0.05 and 1.52 +/- 0.15, p<0.01). Despite BS/GS's higher plasma renin activity and aldosteron a and unchanged level of AT1R, Ang II induced ERK1/2 phosphorylation was reduced vs both C and EH: 0.64 d.u +/- 0.08 vs 0.90 +/- 0.06 in C, p<0.006, and vs 1.45 +/- 0.07 in EH, p<0.001. Conclusion: The data point to a direct cardioremodeling role for Ang II and support a role of Ang II type 2 receptor (AT2R) signaling as involved in the lack of cardiovascular remodeling in BS/GS. However, further studies using more direct approaches o demonstrate the effects of AT2R signaling must be pursued. (J. Endocrinol. Invest. 32: 832-836, 2009) (C)2009, Editrice Kurtis