Efeitos cardiovasculares produzidos pela administração central de lipossomas contendo GABA em modelos de hipertensão

Abstract

Liposomes are spherical microscopic vesicles, consisting of one or more concentric lipid bilayers, which isolate one or more internal aqueous compartments from the external environment and have the capacity to allow the prolonged release of different molecules. GABA (γ-aminobutyric acid) is the main inhibitory neurotransmitter in the central nervous system (CNS). Studies suggest that changes in GABAergic neurotransmission may be associated with the development of cardiovascular diseases, including arterial hypertension (AH). The main objective of the present study was to develop, characterize and test the effects produced by liposomes containing GABA (GL) via previous administration (6 days) via intracerebroventricular (ICV) route on the development of hypertension. Two models were used; 1) spontaneously hypertensive rats (SHR) and, 2) 2 kidney-1 clip rats (2K1C). The liposomes was prepared by the freeze-thaw method, using the following lipids: DSPE, CHO, and DSPE-PEG. The LG had an average size of 160nm and an average encapsulation rate of approximately 21%. SHR and 2K1C rats had systolic blood pressure (SBP) levels above 150 mmHg, characterizing them as hypertensive. When compared to the respective control groups, ICV administration of GL in hypertensive rats: 1) attenuated the development of hypertension in SHR and 2K1C rats, without significant effects on baseline HR; 2) attenuated the pressor response in 2K1C rats and tachycardia to acute stress in SHR and 2K1C rats (stress protocol due to change of environment); 3) reduced anxious behavior in 2K1C rats (marble burying test); 4) did not change muscle strength in 2K1C rats (hang wire test). Regarding central cardiovascular autonomic control, 2K1C animals that previously received ICV administration of GL showed: 5) reduced baseline renal sympathetic nerve activity (RSNA) 6) and attenuation of the increase in RSNA produced by activation (disinhibition) of the paraventricular nucleus of the hypothalamus (PVN). Therefore, our data suggest that a greater bioavailability of central GABA through liposomal vesicles can improve autonomic, cardiovascular, and behavioral parameters inherent to the AH models evaluated. Additionally, our data suggest that GL can be a potential tool to be used in several functional approaches involving the CNS that require central inhibition or assessment of GABAergic neurotransmission.