Nano-formulated anandamide decreases blood pressure, neuroinflammatory and oxidative markers in a rat model of hypertensive disease

FERES MOCAYAR; GARCÍA SEBASTIÁN; VIRNA MARTÍN GIMENÉZ; DIEGO KASSUHA; EMILIANO DIEZ; NATALIA PRADO; ROBERTO YUNES; WALTER MANUCHA

Oldenburg

Congreso; World Congress on Undergraduate Research; 2019

Oldenburg University

Hypertension is considered one of the significant risks of cardiovascular diseases; it is frequently related with: upregulation of the renin-angiotensin system over-excitation of brainstem centers, sympathetic hyperactivation, systemic and neural inflammation. Spontaneously hypertensive rats (SHR) are a validated model of hypertension, plus several neurocognitive deficits. To highlight, the endocannabinoid anandamide (AEA) protects neurons from the inflammatory damage, and cannabinoid signaling decreases in brains of hypertensive animals. However, several side effects were described at the central nervous system level by anandamide; while drugs delivery by nano-formulations could reduce it. Aim: To assess whether nano-formulated anandamide could produce a decrease in blood pressure values as well as a reduction of the systemic inflammatory state and the central nervous system. We used adult male rats normotensive (WKY) and hypertensive (SHR), treated or not with nano-formulated AEA in polycaprolactone (AEA/PCL), at a weekly dose of 5 mg/Kg IP, for four weeks. Systolic blood pressure was obtained by the tail-cuff method. Plus Maze Test and Open Field Test were performed at the end of the treatment. Animals where sacrificed, peripheral blood extracted and frozen, and brain cortex harvested for Western Blot. Inflammatory markers (IL-1, IL-6, TNFα, ultrasensitive CRP and plasma Hsp-70) were dosed in plasma by ELISA. AEA/PCL produced a significant reduction of systolic blood pressure, a decrease in inflammatory markers and oxidative stress markers (NADPH oxidase and nitrites). Protein expression of WT-1, AT-1, and iNOS was higher in SHR brain cortex, while AEA/PCL decreased it. Conversely, Hsp-70 expression increased after treatment within the cerebral cortex. Abnormal behaviors observed in Plus Maze Test (time of permanence in the open arm), and Open Field Test (time of exploration) also decrease after AEA/PCL treatment. These preliminary results suggest antihypertensive and anti-inflammatory properties of AEA. This nano-formulated cannabinoid might regulate inflammation through the AT-1-Hsp-70-iNOS pathway.