Beneficial consequences on myocardial mitochondrial network dynamics and function of one-month oral treatment with cannabis oil to spontaneously hypertensive rats (SHR).

PEREYRA E; GODOY COTO J; CAVALLI F; GONZÁLEZ ARBELÁEZ LF; FANTINELLI JC; ARANDA MOSQUERA JO; COLMAN LERNER E; VELEZ RUEDA JO; MOSCA SM; ENNIS IL

Berlin

Congreso; XXIV World Congress International Society for Heart Research. Junio 2022; 2022

ISHR

IntroductionMitochondrial alterations have been repeatedly linked to a variety of cardiovascular diseases. On the other hand, components of cannabis oil have proved cardioprotective, attenuating inflammatory and oxidative damage. Recently CBD, one of them, was found to regulate mitochondrial status.However, its effect on hypertensive cardiac hypertrophy (CH) and particularly on mitochondrial function, remains elusive. Objective To evaluate cannabis oil treatment on CH and mitochondrial status in SHR hearts.MethodsThree-month old male SHR were randomized into treated (CO) and control (VEH). Cannabis oil or olive oil were orally administered for 1 month. We evaluated CH, myocardial histology, mitochondrial network dynamics by qPCR, mitochondrial membrane potential, myocardialsuperoxide dismutase (SOD), and citrate synthase activity. Data are presented as mean ± SEM (n) and compared by t-Test. P.ResultsCH was significantly reduced by treatment as indicated by the left ventricular weight/tibia length ratio (mg/mm, VEH:33,49 ± 0,2(6); CO:30,47 ± 0,78(9)), left ventricular mass (LVM) by echocardiography at the beginning and end of treatment (Day 0: 943,9 ± 109,4(5) and day 30:921,5 ± 50,96(6) vs day 0: 915,1 ± 41,49(8) day 30: 772,3 ± 21,61 (7), VEH and CO respectively). Furthermore, myocyte cross-sectional area (CSA) and left ventricle collagen volume fraction (LVCVF) were reduced in CO (CSA: 346,4 ± 4,27(4) and 302,1 ± 15,77(5); and LVCVF: 3,460 ± 0,286(4) and 2,495 ± 0,206(4), in VEH and CO respectively). Interestingly, treatment increased endocardial fractional shortening (% VEH:31,59 ± 1,92(5), CO:44,33 ± 4,84(8)) without changing arterial pressure. Mitochondria membrane potential was improved (in mV, VEH: -152,9 ± 2,622(8), CO:- 161,6 ± 2,821(7)), mitochondrial biogenesis enhanced (%ratio of PG1alpha/GAPDH mRNA: VEH:100,0 ± 20,33(6); CO:156,6 ± 13,80(9)) as well as network dynamics (%ratio of gene/GAPDH mRNA: MITO1 VEH:100,0 ± 40,20(4), CO:224,1 ± 18,11(4); PINK VEH:100,0 ± 26,24(5), CO:183,3 ±20,60(8). Moreover, citrate synthase and SOD activities were increased by cannabis oil treatment (% of control VEH:100 ± 6,996(5), CO:119,1 ± 4,556 (8) and VEH:100 ± 19,62(4), CO:269,4 ± 53,31(4), respectively).ConclusionWe propose that one-month oral treatment with Cannabis oil is effective to reduce CH and improve mitochondrial network, probably due to an increased antioxidant capacity.