DIOXIN-LIKE ENVIRONMENTAL TOXIC ALTERS VASCULAR FUNCTION AND BLOOD PRESSURE IN RATS

GORZALCZANY, SUSANA; ROSÓN, MARÍA INÉS; ROMERO CAÍMI, GISELLE; BONAZZOLA, PATRICIA; KLEIMAN, DIANA; CASTILLA, ROCÍO; ALVAREZ, LAURA

Mar del Plata, Buenos Aires , Argentina

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigación Clínica

Hexachlorobenzene (HCB) is anorganochlorine pesticide that induces endocrine dysfunction and alters bloodpressure (BP) in female Wistar rats, as well as thyroid hormones (TH),deiodinase II (DII) and estrogen receptor alpha (ERα), factors involved invascular tone and BP regulation.This study evaluated the effect of HCB onvascular hemodynamics in male Wistar rats to elucidate its mechanism of actionin in vivo and ex vivomodels.In vivo: rats were gavage-administered HCB(5 to 500 mg/kg bw) every 3 days for 45 days. Ex vivo: aorta rings of controlrats were treated with HCB (0.05 and 5µM) for 30 min. The in vivo protocolassessed BP and biochemical markers. Both protocols evaluated histological,biochemical and physiological parameters.In vivo: HCB (500 mg/kg) increased BP (25%,p<0.05) and aortic wall thickness (27%, p<0.05), and decreased cellnumber per area (18%, p <0.05). The toxic also decreased serum T4 (28%,p<0.05), aortic DII mRNA (41%, p<0.001), ERα and eNOS expression (29 and26%, respectively, p<0.05), and increased aorta TGF-b1 mRNA and ATI receptorlevels (39 and 31%, respectively, p<0.01).HCB-treated groups showed decreasedacetylcholine (Ach) aortic relaxation (91.2±3.9, 71.5±3.9, 73.9±3.6, forcontrol, HCB 5mg/kg, HCB 500mg/kg respectively, p<0.01), without changes inphenylephrine (F) contraction or nitroprusside (N) relaxation.In vitro: Aortic rings treated with HCBshowed a decrease in the maximum contraction to F (in mg 3705±167, 2367±149,2650±155 for control, HCB 0.05µM, HCB 5µM, respectively, p<0.01), withoutalterations in relaxation to N. Relaxation to Ach tended to decrease with bothHCB doses.HCB generates hypertension and alters endothelium-dependentrelaxation in male rats, without changes in arterial contraction. DII, ERα andeNOS could be in part involved in the decrease in relaxation, while TGF-b1 andAT1 receptor may be involved in vascular hypertrophy. These findings may explainthe increase in BP in HCB-treated rats.