THE LOSARTAN PREVENTS THE ALTERATIONS CAUSED BY THE ENVIRONMENTAL TOXIC TYPE DIOXIN HEXACLOROBENZENE

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

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argentina de Investigación Clínica

In previous work we showed that environmental dioxine-typehexachlorobenzene (HCB) increases blood pressure (BP) in rats, causingalterations in arterial structure and function. Thyroid hormone, angiotensin IIreceptor type 1 (AT1) and endothelial nitric oxide synthase (eNOS) are involvedin the toxic effect.Here we study whether the AT1 receptorantagonist Losartan (L) can prevent alterations caused by HCB intoxication.Male Wistar rats treated with HCB (500 mg/kgbw) by gastric intubation, 45 days and treated or not with L (30 mg/Kg/day indrinking water). BP was measured during all intoxication period. It wasassessed aortic morphology by analysis of its thickness and cells number and vascularphysiology by arterial contractility in aortic rings contracted withPhenylephrine (P), and relaxed with Acetylcholine (Ach) and Nitroprusside (N)(isometric tension). Molecular markers potentially involved in the mechanism oftoxic action were analyzed by western blot.HCB treated rats showed an increase in BP(145.5±5.1 mmHg) which was prevented by simultaneous administration of L(110.5±8.2 mmHg, p<0.01). HCB decreased the aorta cells number and increase aorticthickness, both effects were partially impaired with L. The maximum contractionby P (% K+ 60mM) decreased which was not altered in L+HCB treatedrats (control: 143±5%, HCB: 123±5%, HCB+L: 122±5%, p<0.05). However, aortasof HCB-treated rats showed less relaxation to Ach stimulus, which was preventedin L+HCB- treated rats. Arteries from HCB treated rats does not show changes  in the N-response curve respect to C group. HCBdecreased PCNA levels (p <0.05) and eNOS (p <0.01) and increased AT1 (p<0.05). L+HCB treatment maintained expression levels of the three parameterssimilar to control.Conclusion: L prevents the increase of BPproduced by HCB intoxication in rats and also the HCB induced alterations in arterialrelaxation endothelium dependent and molecular markers.