RESUMEN
The mechanisms by which pH influences vascular tone are not entirely understood, but evidence suggests that the endothelium is involved. Here, we aimed to study the in vitro vascular responses induced by extracellular hypercapnic acidification (HA), as well as the endothelium-dependent mechanisms that are involved in the responses. We bubbled a mixture of CO2 (40%)/O2 (60%) in an organ bath; we constructed a pH-response curve (pH range 7.4-6.6) and registered isometric force simultaneously. Aortic rings from rats were pre-contracted with phenylephrine (10-6 M) and incubated for 30 min in the presence of different chemicals. The relaxations induced by HA occurred in rings with endothelium were: 1) Partially inhibited by indomethacin (10-5 M) (PGI2 pathway inhibitor); 2) Strongly inhibited by NO pathways: L-NAME (10-4 M) and L-NMMA (10-4 M) (no specific NO synthase inhibitors); L-Nil (10-3 M) (specific iNOS inhibitor); ODQ (10-4 M) (specific guanylate cyclase inhibitor), and; 4) Inhibit by tetraethylammonium (10-3 M) (non-specific potassium channel inhibitor), glibenclamide (10-5 M) (specific KATP inhibitor), aminopyridine (10-3 M) (specific Kv inhibitor) and apamin (10-6 M) (specific SKCa inhibitor). IN CONCLUSION: 1) HA causes endothelium-dependent relaxation; 2) Indomethacin failed in blocking this relaxation, but the method limitation does not allow ruling out some prostanoid role; 3) The HA vessel relaxation is mediated via cGMP/NO, and; 4) The hyperpolarization occurs by the action of potassium SKCa, KATP and Kv channels without relying on BKCa channels.
RESUMEN
BACKGROUND: In acute lung injury (ALI), rupture of the alveolar-capillary barrier determines the protein-rich fluid influx into alveolar spaces. Previous studies have reported that methylene blue (MB) attenuates such injuries. This investigation was carried out to study the MB effects in pulmonary capillary permeability. METHODS: Wistar rats were divided into five groups: (I) Sham: saline bolus; (II) MB, MB infusion for 2 h; (III) oleic acid (OA), OA bolus; (IV) MB/OA, MB infusion for 2 h, and at 5 min after from the beginning, concurrently with an OA bolus; and (V) OA/MB, OA bolus, and after 2 h, MB infusion for 2 h. After 4 h, blood, bronchoalveolar lavage (BAL), and lung tissue were collected from all groups for analysis of plasma and tissue nitric oxide, calculation of the wet weight to dry weight ratio (WW/DW), and histological examination of lung tissue. Statistical analysis was performed using nonparametric test. RESULTS: Although favourable trends have been observed for permeability improvement parameters (WW/WD and protein), the results were not statistically significant. However, histological analysis of lung tissue showed reduced lesion areas in both pre- and post-treatment groups. CONCLUSIONS: The data collected using this experimental model was favourable only through macroscopic and histological analysis. These observations are valid for both MB infusions before or after induction of ALI.