Vasoprotective effects of neurocompensatory response to balloon injury during diabetes involve the improvement of Mas signaling by TGFβ1 activation

Endothelinergic Contractile Hyperreactivity in Rat Contralateral Carotid to Balloon Injury: Integrated Role for ETB Receptors and Superoxide Anion

“…Isoflurane-anaesthetized rats were killed by aortic exsanguination for the remove of common carotid arteries. Carotid rings (4 mm) were placed in organ bath chambers (10 ml) for isolated organs containing 5.0 ml of Krebs-Henseleit bicarbonate buffer (composition in mmol/l: NaCl 118.4; KCl 4.7; CaCl 2 1.9; KH 2 PO 4 1.2; MgSO 4 ·7H 2 O 1.2; NaHCO 3 25; glucose 11.6) gassed with carbogenic mixture (95% O 2 and 5% CO 2 ), kept at 37°C (pH 7.4), and underwent periodic checking [ 14 , 22 , 23 ]. Carotid rings were connected to isometric force transducers (Letica Scientific Instruments, Barcelona, Spain) and underwent a resting tension of 1.0 g, which was readjusted every 15 min throughout a 60 min lasting equilibration period.…”

“…NADPH oxidase-driven O 2 − generation was expressed as relative light unities (RLU) per mg of protein. Protein concentrations were determined with the Bradford assay (BioRad) [ 14 ]. The role of ET B receptors on ET-1-induced NAD(P)H oxidase-driven O 2 − generation was determined in carotid homogenates pretreated with BQ-788 (3.0 μ mol/l), added 30 min before ET-1 (0.1 μ mol/L) stimulation, which was followed by immediate sample freezing [ 26 ].…”

“…Fluorescence emission was detected on the Biotek Synergy HT plate reader at excitation of 530 nm and emission of 590 nm. H 2 O 2 levels were expressed as absolute micromolar concentrations ( μ mol/L) [ 14 ].…”

“…Contractile hyperreactivity of contralateral carotid makes it more sensitive to mechanical load pressure effects of increased vascular resistance conditions, which contributes to a further impairment of cerebral flow already reduced by the ipsilateral restenotic remodeling [ 5 , 14 , 16 ]. Thus, the elucidation of the mechanisms underlying the distant harmful effects of balloon angioplasty has become one of the main clinical interests for overcoming the postoperative complications that limit its therapeutic efficacy.…”

“…Thus, the elucidation of the mechanisms underlying the distant harmful effects of balloon angioplasty has become one of the main clinical interests for overcoming the postoperative complications that limit its therapeutic efficacy. The first findings regarding this matter showed that these effects result from a neurocompensatory response that increases the density of substance P- (SP-) and calcitonin gene-related peptide- (GPCR-) containing nerves at contralateral carotid as an immediate consequence of the damage of perivascular nerve density from ipsilateral carotid during catheter rubbing [ 11 , 14 , 16 ]. In turn, SP and CGRP acutely upregulate the expression of contractile factors underlying α 1 -adrenergic signaling such as cyclooxygenase-2 (COX-2) [ 17 ].…”