CENTRAL NERVOUS SYSTEM, PERIPHERAL AND HEMODYNAMIC EFFECTS OF NANOFORMULATED ANANDAMIDE IN HYPERTENSION

VIRNA MARTÍN GIMENÉZ; FERES MOCAYAR; GARCÍA SEBASTIÁN; LUCIANA MAZZEI; MANUEL GUEVARA; ROBERTO YUNES; WALTER MANUCHA

ADVANCES IN MEDICAL SCIENCES

MEDICAL UNIV BIALYSTOK

Año: 2021 vol. 66 p. 72 - 80

1896-1126

Hypertensive lesions induce alterations at the hemodynamic, peripheral, and central nervous system levels. The endocannabinoid anandamide (AEA) protects neurons from inflammatory damage, but its free administration may cause central adverse effects. Thus, AEA controlled release by nanoformulations could be useful to reduce/eliminate its side effects. We aimed to evaluate the effects of nanoformulated AEA (nf-AEA) on systolic blood pressure (SBP), behavior, and central/peripheral inflammatory, the oxidative and apoptotic state in spontaneously hypertensive rats model (SHR). We used male rats, 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 four 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 levels, and high concentrations of central/peripheral inflammatory/oxidative markers, as well as higher apoptosis of brain cortical cells compared to WKY. In SHR, but not in WKY rats, nf-AEA treatment significantly reduced SBP, as well as 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, the Wilms tumor transcription factor 1, Hsp70 and iNOS. Considering the known pharmacokinetic and pharmacodynamic limitations of non-nf-AEA, this kind of nanoformulations could potentially contribute to the development of new antihypertensive and behavioral disorders treatments associated with hypertension and neuroinflammation.