Fig 1.
Vascular and cardiac effect of BAPN on Ang II induced arterial hypertension.
To assess the effects of Ang II and LOX inhibition on vascular function, we first analyzed the systemic arterial blood pressure measured with tail cuff. A, The systolic arterial blood pressure, B,The mean arterial blood pressure. C, Diastolic arterial blood pressure. n = 6. *P<0.05 compared to control, ƗP<0.05 compared with BAPN group, #P<0.05 compared with Ang II group at their respective day.
Fig 2.
Aortic flow and stiffness characteristics.
The flow characteristics of the lower thoracic aorta, superior to the renal bifurcation, were analyzed with ECHO/Doppler. A, Pulse wave velocity was used to determine vascular stiffness. B, Effective wall stiffness (Eh), was deduced from measuring PWV. C, Wall thickness (h), was measured from perfusion fixed aortas at day 14, at the same location of the PWV readings. D, The effective Young’s modulus (E), readings were made weekly. E, The diastolic flow percentages was calculated comparing the systolic and diastolic VTI’s. F, The reflected wave transit time was measured at the innominate artery with flow Doppler. n = 6. *P<0.05 compared to control, ƗP<0.05 compared with BAPN group, #P<0.05 compared with Ang II group at their respective day.
Fig 3.
Hypertension contributes to vascular stiffness together with structural and material remodeling. Therefore the Alzet pumps were removed to determine the contribution of each to the total vascular stiffness. A, The Alzet pumps were removed on Day 14 and the blood pressure returned to control values by day + 4. B, The pulse wave velocity measured with and without Ang II infusion on days 14 and + 4 days after pump removal. n = 6. *P<0.05 compared to control, ƗP<0.05 compared with Ang II group, #P<0.05 compared with Ang II + BAPN + 4 group.
Fig 4.
Aortic histomorphometry was performed with the elastin specific stain Verhoeff’s Van Gieson (VVG) and the collagen specific stain picrosirius red (PSR). A, Representative histological sections are presented according to treatment. B, The medial thickness and adventitial thickness were analyzed to describe the aortic morphological changes in response to the treatments. C, The aortic structural dimensions as measured with VVG and PSR stains. D, The systolic luminal diameter were measured with the M-mode ECHO, collagen content was quantified with PSR histological staining, and elastin content was measured with VVG stain. n = 6. *P<0.05 compared to control, ƗP<0.05 compared with BAPN group.
Fig 5.
Effect of Ang II and BAPN on LOX, collagen, and cross-linking in aortas.
The effect of LOX is not confined to the crosslinking of collagen and elastin and therefore we examined the effect of LOX on gene expression of other key ECM proteins and enzymes. A, Lysyl-oxidase enzymatic activity measured from the lower thoracic aorta represented by the production of H2O2 and detected by Amplex red oxidation. B, The total collagen content using hydroxyproline concentrations assuming collagen contains 13.5% hydroxyproline. C, Cross-linked collagen, using cyanogen bromide as digestion. D, Percent of collagen cross-linking. n = 6. *P<0.05 compared to control, ƗP<0.05 compared with BAPN group, #P<0.05 compared with Ang II group at their respective day.