In previous work we showed that environmental dioxine-type hexachlorobenzene (HCB) increases blood pressure (BP) in rats, causing alterations in arterial structure and function. Thyroid hormone, angiotensin II receptor type 1 (AT1) and endothelial nitric oxide synthase (eNOS) are involved in this toxic effect. Here we study whether
AT1 receptor antagonist Losartan (L) can prevent alterations caused by HCB intoxication. Male Wistar rats were treated with HCB (500 mg/kg/bw) with or without L (30 mg/kg/day) for 45 days. BP was measured throughout treatment. After 45 days, we analyzed: 1) heart contractile and energetic response by simultaneous mechanical and heat assays in hearts arterially perfused at 37 ºC by Langendorff method, paced at 3 Hz, and exposed to 25 min ischemia followed by 45 min reperfusion (R); 2) kidney function by uremia determination; 3) aortic morphology through thickness and cell number; 4) vascular physiology as arterial contractility in aortic rings contracted with phenylephrine (P), and relaxed with acetylcholine (Ach) and nitroprusside (N) (isometric tension); and 5) molecular markers potentially involved in the mechanism of toxic action 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). Hearts from HCB-treated rats showed a decrease in resting pressure (RP) during R (58.5±4.5 vs 89.2±6.3 mmHg, p<0.05). Neither L nor L+HCB altered RP vs HCB alone (66.5±6.1, 65.33±10.0% for L and L+HCB, respectively). Hearts from HCB- and L-treated rats showed an improvement in post ischemic contractile recovery (46.2±6.0, 39.8±7.4, 18.8±2.3%, for HCB, L and C, respectively, p<0.05 at 45 min of R), which was prevented in L+HCB group (20.2±6.1%, p<0.05 at 45 min of R). HCB did not alter total heat production, while L and L+HCB increased it (83.8±6.5, 79.5±5.6, 56.3±4.7%for L, L+HCB and C, respectively, p< 0.05). Only HCB treatment increased economy during R (67.8±7.2vs. 35.0±5.1%, p<0.05 at 45 min R). Kidney functions remained unaltered in all treatments. HCB decreased aorta cell number (36.6% p<0.01) and increased thickness (23%, p<0.05), and both effects were partially impaired by L. The maximum contraction by P (% K+ 60 mM) decreased with HCB and did not recover in L+HCB treated rats (control: 143±5%, HCB: 123±5%, HCB+L: 122±5%, p<0.05). Aorta relaxation by Ach was reduced in HCB-treated rats but remained unaltered in the L+HCB group. Arteries from HCB-treated rats did not show changes in the N response with respect to C group. HCB decreased PCNA (p<0.05) and eNOS (p<0.01) and increased AT1 (p<0.05) expression levels. L+HCB treatment maintained expression levels of the three parameters similar to control. Conclusion: L prevents the increase in BP and alterations in heart, endothelium-dependent arterial relaxation and molecular markers in rats exposed to HCB intoxication.