LOSARTAN IMPAIRS HEXACHLOROBENCENE-INDUCED HYPERTENSION AND MODIFY THE MECHANO-ENERGETIC RESPONSE OF RAT HEARTS TO ISCHEMIA/REPERFUSION INJURY.

BONAZZOLA, PATRICIA; CAIMI, GISELLE; VILLA ETCHEGOYEN, CECILIA; ROSÓN, MARÍA INÉS; GORZALCZANY, SUSANA; ALVAREZ, LAURA; CASTILLA, ROCÍO

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argentina de Investigación Clínica

We have shown that the bio-accumulated organ chlorinadepesticide hexachlorobenzene (HCB) produces hypertension (Hyp) in rats, probablythrough an increase in arterial angiotensine II receptor 1 (AT1) expression. Alsowe showed an increase in post ischemic contractile recovery (PICR) and economyfor contraction (Eco) in isolated hearts from HCB-treated rats, a potential adaptative response to pesticide-induced Hyp.Here, we study the role of AT1 in HCB-inducedHyp by means of AT1 antagonist Losartan (L) treatment,focusing on heart contractile and energeticresponse to an ischemic insult.Male Wistar rats were treated with 500 mg/kg HCB andwith 30 mg/kg L for 45 days. Hearts were used for histological analysisor mechanical and energy assays. To this end, simultaneous mechanical and heatmeasurements were done in hearts arterially perfused at 37ºC by Langendorff method, paced at 3 Hz, and exposedto 25 min ischemia followed by 45 min. reperfusion (R).L prevented HCB-induced Hyp (110.5±8.2, vs 145.5±5.1mmHg, p<0.05). Hearts from HCB-treated rats showed adecrease 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).An improvement of PICR was observedin hearts from HCB- and L-treated rats (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). L+HCB prevented theHCB-induced increase in PICR (20.2±6.1%, p<0.05 at 45 min of R).HCB did not alter total heatproduction (Ht), 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). HCB increased Eco during R (67.8±7.2vs. 35.0±5.1%, p<0.05 at 45 min R) and neither L nor L+HCB modified it. Conclusion: L diminished HCB-induced Hyp. The impairmentby L of cardiac HCB-induced mechanic and energetic effects suggests that HCB heartprotection is a response to HCB-induced Hyp