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Advanced Neurologyurology
Advanced Ne Brain AT -R and kidney crosstalk
1

through AT -R is involved in renal sodium homeostasis an increase in brain ANG II and SNS activity. Intra- and
1
under normal and pathological conditions in close relation extra-renal interactions between the renin-angiotensin
to the sympathetic nervous system (SNS). The anatomical system and RSNA are involved in the neural control
[6]
and physiological evidence shows that sympathetic of renal function . ANG II through AT -R placed in
1
nerves innervate the juxtaglomerular cells, renal tubules, kidney tubules and vessels exert direct actions on sodium,
and vasculature [6,7] . Hence, the frequency of the renal chlorine, and water reabsorption, as well as in vascular
sympathetic nerve activation (RSNA) mediates the increase constriction .
[6]
in sodium and water excretion regulating tubular renal Considering the above-mentioned evidence, we aimed
water and sodium reabsorption in the nephron, promoting to evaluate the brain AT -R’s role in renal function mediated
1
changes in renal function, blood flow, and glomerular by its interaction with SNS under two independent
filtration rate. However, any change in water and sodium conditions: Sham or renal denervation. The hypersodic diet
intake can modify their excretion and absorption. The SNS was used to inhibit peripheral ANG II while stimulating
regulates renal vasculature vasoconstriction and peripheral brain ANG II. This condition can unmask the brain AT -R
ANG II generation by renin release from juxtaglomerular influence over SNS under surgical renal denervation . 1
[22]
cells [8,9] .
Cardiovascular and hydrosaline homeostasis 2. Materials and methods
maintenance requires fine coordination between the 2.1. Animals
neuroendocrine and autonomic systems. The central Male Wistar rats (250–300g) were used. The animals
nervous system (CNS) receives information from multiple were maintained under controlled environmental
sensors (osmolarity, pH, pressure, blood volume, and conditions (20–24 C, 12 h light/dark cycle with lights on
o
circulating hormones) and integrates the signals generating at 7 a.m.) with ad libitum access to food and water and
adaptive responses . The hydromineral and osmotic were randomly housed in groups of 5 per cage (34 × 48
[10]
regulation depend on arginine-vasopressin (AVP) and × 19 cm). All procedures were approved by the Animal
oxytocin released from the supraoptic nucleus (SON) and Care and Use Committee of the Facultad de Ciencias
paraventricular nucleus (PVN) which both playing a key Químicas, Universidad Nacional de Córdoba, Argentina
role in sodium and water excretion . The osmotic sensors (Res. No. 270/18), in accordance with the NIH Guide for
[11]
are in the subfornical (SFO) and organum vasculosum of the Care and Use of Laboratory Animals.
the lamina terminalis (OVLT), placed outside the blood-
brain barrier [12-14] . Moreover, there are direct and indirect 2.2. Drugs
interactions between SNS and CNS through specific The selective AT -R antagonist, losartan (Los, Sigma
innervation or mediation by ANG II that regulate renal Aldrich), was dissolved in artificial cerebrospinal fluid
1
sympathetic activity. Evidence shows that the increase in (ACF). The solution was freshly used, protected from
the RSNA can be blunted with angiotensin-converting light, and kept at 4°C. The dose (4 µg/µL) was selected
enzyme inhibitors (ACEI) or AT -R antagonists . In the considering previous studies [23-25] .
[6]
1
same way, the effects of ANG II intrarenal administration
are decreased after renal denervation . The interactions 2.3. Experimental design
[6]
are modulated by changes in the renin-angiotensin system In this work, a 6-day protocol with animals receiving
activation that control RSNA and its arterial baroreflex . normal sodium (0.4%) or high sodium (4%) diet was
[15]
The kidney is the target for oxytocin and AVP hormones performed. Stereotaxic surgery was executed on day 1,
that control water and sodium excretion, released in Los was administered on day 5 in the right and left lateral
response to hypovolemia or hyperosmolarity [16,17] . In ventricles, and 12 h after Los administration, plasma,
addition to its neuroendocrine actions, AVP induces a fast kidney, and SNC samples were taken (Figure 1).
and enduring increase in SNS activity [18,19] .
In addition to the effects induced by circulating ANG 2.4. Surgery for cannulae implantation and
II on circumventricular organs, the effects inside the denervation
blood-brain barrier are mediated by local ANG II [20,21] . Animals were anesthetized with ketamine (75 mg/kg,
It has been found that central administration of AT -R Holliday)/xylazine (5 mg/kg, Köing) intraperitoneal
1
antagonist can modulate changes in brain ANG II activity administration (i.p.). In aseptic conditions, rats’ skulls
induced by physiological alterations in sodium intake. This were exposed, and a bilateral stainless steel cannula (23
modulation was also observed in a physiopathological gauge) was implanted using a stereotaxic device fixed with
model (congestive cardiac insufficiency), where there is dental cement (Subiton, Argentina). Furthermore, one

Volume 2 Issue 2 (2023) 2 https://doi.org/10.36922/an.393