NDT Advance Access published online on March 14, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn118
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Absence of vascular remodelling in a high angiotensin-II state (Bartter's and Gitelman's syndromes): implications for angiotensin II signalling pathways
1 Department of Clinical and Experimental Medicine, University of Padova, Italy 2 Department of Nutrition, University of California, Davis, CA, USA
Correspondence and offprint requests to: Lorenzo A. Calò, Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy. Tel: +39-049-8218701 and +39-049-8212279; Fax: +39-049-8754179; E-mail: renzcalo{at}unipd.it
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Abstract |
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Background. Angiotensin II (Ang II) is a powerful proinflammatory cytokine and growth factor that activates NF-
B, as well as NAD(P)H oxidase, and thus is a key factor for the induction and progression of cardiovascular diseases. Our previous studies have shown high Ang II and high blood pressure-driven proatherogenic remodelling in an animal model. To further explore Ang II in proatherogenic vascular remodelling independent of blood pressure, we used Bartter’s/Gitelman's syndrome (BS/GS) patients given their elevated plasma Ang II, yet normo/hypotension, because extensive mechanistic studies in these patients suggest they are a good model to explore Ang II-mediated signalling.
Methods. The study evaluated BS/GS patients for nitric oxide-dependent (FMD) and -independent vasodilation and intima-media thickness (IMT) of the carotid arteries compared with healthy subjects and essential hypertensive patients.
Results. The results showed the absence of IMT growth in BS/GS patients as cumulative mean-IMT and mean maximum-IMT levels in BS/GS did not differ from normotensives: 0.58 ± 0.09 mm versus 0.60 ± 0.09 and 0.67 ± 0.09 versus 0.70 ± 0.13 respectively, P = ns, but were significantly lower compared with hypertensive patients: 0.69 ± 0.13, P < 0.046 and 0.85 ± 0.19, P < 0.018, respectively. FMD was increased in BS/GS versus hypertensives or normotensive controls (10.8 ± 2.7% versus 6.5 ± 2.3 and 8.7 ± 1.9, P < 0.002 respectively) while endothelium-independent dilation did not differ (10.2 ± 3.6% versus 7.2 ± 1.9 and 8.2 ± 3.3, P = ns) between groups.
Conclusions. Our study in BS/GS provides to our knowledge the first clinical data that point to a direct proatherogenic role for Ang II. However, because the data are derived from findings in BS/GS and therefore are indirect, further studies in this and other models using more direct approaches should be pursued to demonstrate a direct proatherogenic effect of Ang II as well as further studies on Ang II type 2 receptor (AT2R) signalling that the spectrum of findings of this and other studies indicate as involved in the lack of vascular remodelling.
Keywords: angiotensin II; Gitelman's syndrome; intima–media thickness; NO dependent dilation; vascular remodeling
Received for publication: 4.12.07
Accepted in revised form: 11. 2.08