Indole-3-carbinol reduces cardiovascular remodeling and arrhythmias linked to hypertension

MARIANA CASAROTTO; VANESA BERETTA; EMILIANO DIEZ; MICAELA PARRA; DARÍO CUELLO-CARRIÓN; AMIRA PONCE ZUMINO; JUAN PABLO CALVO; ALEJANDRA CAMARGO; WALTER MANUCHA

Mendoza

Simposio; XIV Jornadas de Investigación FCM y del II Simposio de Medicina Traslacional.; 2019

IntroductionHypertension and cardiac arrhythmias stand out as one of the leading causes of morbidity and mortality. Inflammation and oxidative damage are critical factors in the pathogenesis of both entities. In this sense, alterations of molecular mediators such as nitric oxide (NO) and heat shock protein 70 (Hsp70), would determine a proarrhythmogenic cardiac remodeling during hypertension (HT). Of interest, it has been described that a diet with a low content of certain phytochemicals could worsen hypertensive remodeling through inflammation and oxidative stress, which consequently increases the incidence of cardiovascular diseases (CVD).With special attention to the substances known as phytochemicals -present in the so-called functional foods- and that among their protective functions have been reported a reduction of inflammation and oxidative stress. In parallel, recent research suggests that the modulation of this signaling pathway, through the use of functional foods, is a valuable strategy in the prevention of CVD. In this sense, and of particular interest for the present work, it has been lately reported that indole-3-carbinol (I3C) present in cruciferous vegetables (broccoli and cabbage), would protect against the inflammatory response caused by ischemia-reperfusion (IR). However, the mechanisms involved in this inflammatory condition are not known in depth and, even less, the possible implications on the arrhythmogenic events of IR.AimsTo evaluate, in the physiopathological condition from acute coronary ischemia/reperfusion, the electrophysiological and structural changes, as well as, possible signaling pathways involved in the protection mediated by chronic I3C treatment.MethodsThe authors confirm that during the development of the protocol with animals, we agreed with the regulations of the Institutional Committee for the Care and Use of Laboratory Animals of the Faculty of Medical Sciences of the UNCuyo. We perform the study in male SHR and WKY rats, that received or not I3C (2000 ppb/day, VO) from birth to 8 weeks of life (n = 10, for each group). In all cases, blood pressure records (CODA) were taken. After the 8 weeks, five cardiac samples were collected for histology (Masson's trichrome, eosin hematoxylin, histochemistry, and TUNEL). Also, tissues were separated for molecular assays (proteins expression of interest by western blot technique), and peripheral blood was collected to evaluate inflammatory molecular markers. In simultaneous, five isolated hearts were used for the IR protocol, which were perfused according to the Langendorf technique with a Krebs Henseleit modified solution containing in mM: 121 NaCl; 5 KCl; 2.25 CaCl2; 1.2 MgSO4; 1.2 NaHPO2; 25 NaHCO3; 11 glucose, carbogen gassed (5% CO2 and 95% O2), and at 36.5 ± 0.5 ºC. In the hearts of the WKY rats, the perfusion pressure was kept constant at 80 cm H20, whereas in the SHR rats it was raised to 120 cm H20. After 20 min of stabilization and 10 min of pre-ischemia, a regional ischemia (by ligation of the anterior descending coronary artery) of 10 min was performed. Then it was re-perfused for 10 min. Finally, we evaluate the action potentials, the electrocardiogram and the arrhythmias (incidence and severity).ResultsThe SHR rats showed histological, structural and functional changes with a significant increase in systolic blood pressure (WKY=121±3 mmHg, SHR=151±5 mmHg; P