Central nervous system, peripheral and hemodynamic effects of nanoformulated anandamide in hypertension

• Published in: Advances in medical sciences 2021-03, Vol.66 (1), p.72-80
• Main Authors: Martín Giménez, Virna Margarita, Mocayar Marón, Feres José, García, Sebastián, Mazzei, Luciana, Guevara, Manuel, Yunes, Roberto, Manucha, Walter
• Format: Article
• Language: English
• Subjects: Anandamide; Hypertension; Inflammation; Nanoformulation; Oxidative stress
• ISSN: 1896-1126; 1898-4002
• DOI: 10.1016/j.advms.2020.12.003

Hypertensive lesions induce alterations at hemodynamic, peripheral, and central levels. Anandamide (N-arachidonoylethanolamine; AEA) protects neurons from inflammatory damage, but its free administration may cause central adverse effects. AEA controlled release by nanoformulations could reduce/eliminate its side effects. The present study aimed to evaluate the effects of nanoformulated AEA (nf-AEA) on systolic blood pressure (SBP), behavior, and central/peripheral inflammatory, oxidative, and apoptotic state in spontaneously hypertensive rats (SHR). Male rats were used, both Wistar Kyoto (WKY) and SHR (n ​= ​10 per group), with/without treatment with nf-AEA (obtained by electrospraying) at a weekly dose of 5 ​mg/kg IP for 4 weeks. SBP was measured and behavioral tests were performed. Inflammatory/oxidative markers were quantified at the central (brain cortex) and peripheral (serum) level. SHR showed hyperactivity, low anxiety, and high concentrations of central/peripheral inflammatory/oxidative markers, also higher apoptosis of brain cortical cells compared to WKY. As opposed to this group, treatment with nf-AEA in SHR significantly reduced SBP, peripheral/central inflammatory/oxidative makers, and central apoptosis. Nf-AEA also increased neuroprotective mechanisms mediated by intracellular heat shock protein 70 (Hsp70), which were attenuated in untreated SHR. Additionally, nf-AEA reversed the abnormal behaviors observed in SHR without producing central adverse effects. Our results suggest protective properties of nf-AEA, both peripherally and centrally, through a signaling pathway that would involve the type I angiotensin II receptor, Wilms tumor transcription factor 1, Hsp70, and iNOS. Considering non-nf-AEA limitations, this nanoformulation could contribute to the development of new antihypertensive and behavioral disorder treatments associated with neuroinflammation. [Display omitted]