Key result
Bartter's/Gitelman's syndrome patients had lower cumulative mean carotid intima-media thickness compared with hypertensive patients (0.58 vs 0.69 mm, P<0.046) despite high Angiotensin II.
Cross-Sectional
Absolute Event Rate: 0.58% vs 0.69%
p-value: p=<0.046
Patients with Bartter's/Gitelman's syndrome lack proatherogenic vascular remodeling despite high Angiotensin II levels, suggesting blood pressure-independent mechanisms or AT2R signaling involvement.
Suggests BP-independent vascular protection in Bartter's/Gitelman's; leaves open mechanistic roles of Ang II signaling for targeted research.
BACKGROUND: Angiotensin II (Ang II) is a powerful proinflammatory cytokine and growth factor that activates NF-kappaB, 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.
No takes yet. Share an insight, caveat, or question.
Calò et al. (2008) conducted a cross-sectional in Bartter's and Gitelman's syndromes. Bartter's/Gitelman's syndrome (high Angiotensin II state) vs. Healthy normotensive subjects and essential hypertensive patients was evaluated on Cumulative mean intima-media thickness (IMT) of the carotid arteries (p=<0.046). Bartter's/Gitelman's syndrome patients had lower cumulative mean carotid intima-media thickness compared with hypertensive patients (0.58 vs 0.69 mm, P<0.046) despite high Angiotensin II.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: