Abstract | 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.
|
Authors | Lorenzo A Calò, Massimo Puato, Silvia Schiavo, Marco Zanardo, Carmen Tirrito, Elisa Pagnin, Giulia Balbi, Paul A Davis, Paolo Palatini, Paolo Pauletto |
Journal | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
(Nephrol Dial Transplant)
Vol. 23
Issue 9
Pg. 2804-9
(Sep 2008)
ISSN: 1460-2385 [Electronic] England |
PMID | 18344243
(Publication Type: Journal Article)
|
Chemical References |
- Receptors, Drug
- SLC12A3 protein, human
- Solute Carrier Family 12, Member 3
- Symporters
- Angiotensin II
|
Topics |
- Adult
- Angiotensin II
(physiology)
- Bartter Syndrome
(pathology, physiopathology)
- Carotid Arteries
(diagnostic imaging, pathology)
- Endothelium, Vascular
(physiopathology)
- Female
- Gitelman Syndrome
(genetics, pathology, physiopathology)
- Humans
- Hypertension
(pathology)
- Male
- Middle Aged
- Receptors, Drug
(genetics)
- Signal Transduction
(physiology)
- Solute Carrier Family 12, Member 3
- Symporters
(genetics)
- Tunica Intima
(pathology)
- Tunica Media
(pathology)
- Ultrasonography
- Vasodilation
(physiology)
- Young Adult
|