title: Absence of vascular remodelling in a high angiotensin-II state (Bartter's and Gitelman's syndromes): implications for angiotensin II signalling pathways.
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.affiliation: Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy. renzcalo@unipd.it
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Calò
authors.forename: Massimo
authors.initials: M
authors.lastname: Puato
authors.forename: Silvia
authors.initials: S
authors.lastname: Schiavo
authors.forename: Marco
authors.initials: M
authors.lastname: Zanardo
authors.forename: Carmen
authors.initials: C
authors.lastname: Tirrito
authors.forename: Elisa
authors.initials: E
authors.lastname: Pagnin
authors.forename: Giulia
authors.initials: G
authors.lastname: Balbi
authors.forename: Paul A
authors.initials: PA
authors.lastname: Davis
authors.forename: Paolo
authors.initials: P
authors.lastname: Palatini
authors.forename: Paolo
authors.initials: P
authors.lastname: Pauletto
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000502:physiology*; D001477:Bartter Syndrome / Q000473:pathology / Q000503:physiopathology*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D053579:Gitelman Syndrome / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011955:Receptors, Drug / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D014463:Ultrasonography; D014664:Vasodilation / Q000502:physiology; D055815:Young Adult
chemical_list: D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D000804:Angiotensin II