Increased production of reactive oxygen species (ROS) in brain regions contributes to the sympathetic vasomotor overactivity in Goldblatt hypertension (2K1C). Previously, studies reported that overexpression of spinal angiotensin II (Ang II) type I (AT1) contributes to sympathetic vasomotor overactivation in 2K1C rats. Considering that Ang II leads to an imbalance of oxidative stress, the present study evaluated the role of spinal ROS in regulating the activity of sympathetic preganglionic neurons in 2K1C rats. Hypertension was induced by clipping the left renal artery. Six weeks after clipping, a catheter was inserted into the subarachnoid space and advanced to the T10-11 vertebral level in urethane-anaesthetized rats. The effects of intrathecal (i.t.) injection of Tempol on mean arterial pressure (MAP), heart rate (HR), renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively) were evaluated over 60 consecutive minutes. mRNA expression of enzymes involved in oxidative balance was analyzed in the spinal cord. In addition, spinal ROS abundance was quantified by the DHE fluorescence method. An increase in ROS production was observed in the thoracic region of 2K1C rats compared to the control group. I.t. administration of Tempol triggered a significant and preferential reduction in rSNA in the 2K1C but not in control rats. Thus, the data suggest that renal sympathoexcitation in 2K1C rats was associated with an increase in oxidative imbalance in the spinal cord, particularly in sympathetic preganglionic neurons that drive rSNA.

The Goldblatt model of hypertension (2K-1C) in rats is characterized by renal sympathetic nerve activity (rSNA). We investigated the effects of unilateral renal denervation of the clipped kidney (DNX) on sodium transporters of the unclipped kidneys and the cardiovascular, autonomic, and renal functions in 2K-1C and control (CTR) rats. The mean arterial pressure (MAP) and rSNA were evaluated in experimental groups. Kidney function and NHE3, NCC, ENaCβ, and ENaCγ protein expressions were assessed. The glomerular filtration rate (GRF) and renal plasma flow were not changed by DNX, but the urinary (CTR: 0.0042 ± 0.001; 2K-1C: 0.014 ± 0.003; DNX: 0.005 ± 0.0013 mL/min/g renal tissue) and filtration fractions (CTR: 0.29 ± 0.02; 2K-1C: 0.51 ± 0.06; DNX: 0.28 ± 0.04 mL/min/g renal tissue) were normalized. The Na+/H+ exchanger (NHE3) was reduced in 2K-1C, and DNX normalized NHE3 (CTR: 100 ± 6; 2K-1C: 44 ± 14, DNX: 84 ± 13%). Conversely, the Na+/Cl− cotransporter (NCC) was increased in 2K-1C and was reduced by DNX (CTR: 94 ± 6; 2K-1C: 144 ± 8; DNX: 60 ± 15%). In conclusion, DNX in Goldblatt rats reduced blood pressure and proteinuria independently of GRF with a distinct regulation of NHE3 and NCC in unclipped kidneys.

La litiasis renal (LR) es una enfermedad de alta prevalencia mundial. Los estudios indican que existe una correlación entre la presencia de LR y el desarrollo de enfermedades cardiovasculares. Investigar el posible papel del sistema nervioso autónomo (SNA) en el riesgo cardiovascular (RCV) de pacientes con LR. Se incluyeron 19 pacientes diagnosticados de LR y 21 individuos sin LR en el grupo control (CTL). Se evaluaron las presiones arteriales sistólica (PAS), diastólica (PAD) y media (PAM), frecuencia cardíaca (FC) en reposo y en respuesta a desafíos cardiovasculares, como ortostatismo y prueba de Stroop. Se realizaron análisis bioquímicos en sangre y orina 24 horas, de todos los participantes del estudio, reclutamiento en la consulta externa de nefrología/ litiasis renal en el periodo de 2017-2019. El grupo LR presentó mayores niveles de colesterol LDL (102,9±24,0 vs 92,4±33,0 mg/dL, p=0,02), glicemia (87,5±8,5 vs 80,3±7,3 mg/dL, p=0,003) y volumen urinario (1966±789 vs 1600±574 mL, p=0,006). El grupo con LR presentó valores más altos de PAS y PAD durante el ortostatismo en comparación con el grupo CTL (PAS: 126±15 vs 122±9 mmHg, p<0,05 y PAD: 81±8 vs 79±7 mmHg, p<0,05, LR vs CTL, respectivamente). En la prueba de Stroop, en el análisis de los deltas absolutos de PAS (9±10 vs 2±8 mmHg, p<0,05) y FR (13±7 vs 8±7 lpm, p<0,05), el grupo LR presentó valores más altos. Se encontró evidencia de posibles alteraciones autonómicas en respuesta al ortostatismo y a la prueba de Stroop, que podrían estar relacionadas con el papel del SNA en el CVR de pacientes con LR. Palabras clave: litiasis renal, barorreflejo, estrés fisiológico, presión arterial, riesgo cardiovascular, sistema nervioso autónomo.

ABSTRACT The activation of specific brain areas involved in regulating the vasomotor sympathetic activity can lead to distinct effects in the postganglionic nerves in both physiological and pathological conditions, suggesting that the sympathetic vasomotor activity is differentially coded depending on the nerve outflow and the target organs. Previous studies investigating such patterns have mostly focused on the global energy of the signal. However, recent evidence has suggested that relevant information is coded in the power distribution along the frequency range. Disturbing the sympathoexcitatory vasomotor tone in the paraventricular nucleus of the hypothalamus (PVN) allows to investigate the sympathetic nerve activity in overloaded conditions in both hypertensive and control animals. By disinhibiting the PVN through the microinjection of bicuculline, an antagonist of γ-aminobutyric acid type A (GABAa) receptors, in the Goldblatt (2K1C) rat model of hypertension we addressed the territorially differential changes in the frequency parameters of the renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively). We also tested the effect of the systemic administration of losartan, an antagonist of the angiotensin II type 1 receptors (AT1), in the attenuation of the increased rSNA and sSNA in 2K1C rats, once these changes are reported to be dependent on the AT1 activation in the Goldblatt model. Our results revealed that each nerve activity presents its own electrophysiological pattern of frequency-coded rhythm in each group, in basal condition and after bicuculline microinjection, but with no significant differences regarding total power comparison among groups. Additionally, the 2K1C animals treated with losartan showed no decrease in the hypertensive response triggered by the GABAa antagonism when compared to the non-treated 2K1C group. However, their spectral patterns of sympathetic nerve activity were different from the other two groups, suggesting that the systemic blockade of AT1 receptors does not totally recover the basal levels of neither the autonomic symptoms nor the electrophysiological patterns in the Goldblatt model, but act on their spectral frequency distribution. These results suggest that the differential responses evoked by the PVN were preferentially coded in frequency of vasomotor sympathetic responses, indicating that the PVN distinctly modulated each rhythmic activity. Financial Support – FAPESP (2019/25295-0)

Natalia Cuevas1,2, Andrea Salamanca 2, Natalia Rodríguez-Romero 3,4, Gerardo Weisstaub 5, Ruy R. Campos6, and Iván Rodríguez-Núñez3,4* 1Pediatric Intensive Care Unit, Hospital Exequiel González Cortés, Santiago, Chile; 2School of Kinesiology, Faculty of Health Science, Universidad de San Sebastián, Concepcion, Chile; 3Laboratory of Movement Physiology, Department of Kinesiology, Universidad de Concepción, Concepcion, Chile; 4Service of Kinesiology, Science and Society Foundation, Concepcion, Chile; 5Public Nutrition Unit, INTA, Universidad de Chile, Santiago, Chile; 6Laboratory of Cardiovascular Physiology, Department of Fisiology, Universidade Federal de São Paulo, São Paulo, Brazil SCIENTIFIC LETTER

Several neurohumoral factors contribute to cardiovascular dysfunction in obesity. In this study, we tested the influence of retroperitoneal white adipose tissue (rWAT) innervation on baroreflex control of blood pressure, inflammation in target organs and renal function markers in an experimental model of overweight in rats with increased sympathetic drive. Wistar rats were treated with high-fat diet (HFD) for 8 weeks and underwent surgical rWAT denervation (DNX) at 6 weeks (n=6/group). At the end of the experimental protocol, we found that DNX improved reflex bradycardia (HFD: -1.76 ± 0.19, HFD+DNX: -2.76 ± 0.20, Control: -2.36 ± 0.12 bpm/mmHg) and decreased hepatic and splenic proinflammatory cytokines in the HFD group. Moreover, serum angiotensinogen (HFD: 112 ± 10 vs HFD+DNX: 84 ± 12 uM) and leptin (HFD: 9.8 ± 1.2 vs HFD+DNX: 5.2 ± 0.8 ng/dL) were decreased after DNX. No change was found in renal cytokines or function markers. Therefore, these findings suggest that neural signaling from the rWAT contributes to cardiovascular changes and inflammation in target organs in rats treated with HFD. CAPES, CNPq and FAPESP This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Chronic kidney disease (CKD) is characterized by progressive and irreversible loss of kidney function. The main causes of CKD are arterial hypertension (AH) and type 2 diabetes. Previous studies by our group showed that renal denervation (DNx) decreased arterial hypertension and sympathetic overactivity in rats with CKD. In the present study, we studied the renoprotective and cardiovascular effects of DNx associated or not with renin-angiotensin system (RAS) blockade. Wistar rats underwent experimental CKD induction (⅚ nephrectomy model). After 4 weeks of CKD induction, we performed DNx and collected data after 4 weeks. Groups that underwent RAS blockade were treated orally with losartan (30mg/kg/day) in the last 4 weeks of the 8-week protocol. Losartan decreased arterial pressure (118±21 mmHg) compared to CKD group (175±18 mmHg). However, the association of losartan treatment with DNx was able to normalize this parameter (94±9mmHg). In addition, losartan normalized baseline renal sympathetic nerve activity, and DNX associated or not with losartan normalized splanchnic sympathetic nerve activity. Interestingly, lipocalin associated with neutrophil gelatinase (NGAL), an important marker of tubular injury, and an intrarenal RAS marker were normalized after DNx associated with losartan treatment (70.9±23.8 NGAL:Cru) or not (66.6±17.8 NGAL:Cru) was normalized. Treatments unchanged water intake or urinary flow. Taken altogether, our data show that despite the association of DNx and RAS blockade produces a further decrease in AH, the improvement in renal function markers and normalization in intrarenal RAS and sympathetic drive is similar after DNx or RAS blockade alone. FINANCIAL SUPPORT: CAPES, FAPESP and CNPq This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Introduction:The paraventricular nucleus of the hypothalamus (PVN) contains premotor neurons involved in the control of sympathetic vasomotor activity. It is known that the stimulation of specific areas of the PVN can lead to distinct response patterns at different target territories. The underlying mechanisms, however, are still unclear. Recent evidence from sympathetic nerve recording suggests that relevant information is coded in the power distribution of the signal along the frequency range. In the present study, we addressed the hypothesis that the PVN is capable of organizing specific spectral patterns of sympathetic vasomotor activation to distinct territories in both normal and hypertensive animals. Methods:To test it, we investigated the territorially differential changes in the frequency parameters of the renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively), before and after disinhibition of the PVN by bicuculline microinjection. Subjects were control and Goldblatt rats, a sympathetic overactivity-characterized model of neurogenic hypertension (2K1C). Additionally, considering the importance of angiotensin II type 1 receptors (AT1) in the sympathetic responses triggered by bicuculline in the PVN, we also investigated the impact of angiotensin AT1 receptors blockade in the spectral features of the rSNA and sSNA activity. Results:The results revealed that each nerve activity (renal and splanchnic) presents its own electrophysiological pattern of frequency-coded rhythm in each group (control, 2K1C, and 2K1C treated with AT1 antagonist losartan) in basal condition and after bicuculline microinjection, but with no significant differences regarding total power comparison among groups. Additionally, the losartan 2K1C treated group showed no decrease in the hypertensive response triggered by bicuculline when compared to the non-treated 2K1C group. However, their spectral patterns of sympathetic nerve activity were different from the other two groups (control and 2K1C), suggesting that the blockade of AT1 receptors does not totally recover the basal levels of neither the autonomic responses nor the electrophysiological patterns in Goldblatt rats, but act on their spectral frequency distribution. Discussion:The results suggest that the differential responses evoked by the PVN were preferentially coded in frequency, but not in the global power of the vasomotor sympathetic responses, indicating that the PVN is able to independently control the frequency and the power of sympathetic discharges to different territories.

OXYGEN IN THE COVID-19 CONTEXT: WHAT WE KNOW ABOUT THE MOLECULE WE BREATHE AND THE CENTRAL ROLE OF CHEMISTRY. In this work, the role of chemistry in the coronavirus disease 2019 (COVID-19) pandemic is highlighted through the medical oxygen supply crises in Brazil, as an example of oxygen utility in health. Starting from oxygen chemical characterization, the oxygen cycle in nature is discussed to show how oxygen is formed through photosynthesis, followed by the description of the industrial oxygen production from atmospheric air, including physical-chemical aspects. The use of medical oxygen concentrator is presented and how this device works from the chemical point of view. Besides, the noninvasive and painless oximetry is described in terms of how oxygen saturation level in blood is measured using LED - light emitting diode.

We examined the effects of an acute increase in blood pressure (BP) and renal sympathetic nerve activity (rSNA) induced by bicuculline (Bic) injection in the paraventricular nucleus of hypothalamus (PVN) or the effects of a selective increase in rSNA induced by renal nerve stimulation (RNS) on the renal excretion of sodium and water and its effect on sodium-hydrogen exchanger 3 (NHE3) activity. Uninephrectomized anesthetized male Wistar rats were divided into three groups: (1) Sham; (2) Bic PVN: (3) RNS + Bic injection into the PVN. BP and rSNA were recorded, and urine was collected prior and after the interventions in all groups. RNS decreased sodium (58%) and water excretion (53%) independently of BP changes (p < 0.05). However, after Bic injection in the PVN during RNS stimulation, the BP and rSNA increased by 30% and 60% (p < 0.05), respectively, diuresis (5-fold) and natriuresis (2.3-fold) were increased (p < 0.05), and NHE3 activity was significantly reduced, independently of glomerular filtration rate changes. Thus, an acute increase in the BP overcomes RNS, leading to diuresis, natriuresis, and NHE3 activity inhibition.

Chronic nicotine exposure may increase cardiovascular risk by impairing the cardiac autonomic function. Besides, physical exercise (PE) has shown to improve cardiovascular health. Thus, we aimed to investigate the effects of PE on baroreflex sensitivity (BRS), heart rate variability (HRV), and sympathetic nerve activity (SNA) in chronically nicotine-exposed rats. Male Wistar rats were assigned to four independent groups: Control (treated with saline solution), Control+Ex (treated with saline and submitted to treadmill training), Nicotine (treated with Nicotine), and Nicotine+Ex (treated with nicotine and submitted to treadmill training). Nicotine (1 mg.kg(-1)) was administered daily for 28 consecutive days. PE consisted of running exercise (60%-70% of maximal aerobic capacity) for 45 min, 5 days per week, for 4 weeks. At the end of the protocol, cardiac BRS, HRV, renal SNA (rSNA), and renal BRS were assessed. Nicotine treatment decreased absolute values of HRV indexes, increased low frequency/high frequency ratio of HRV, reduced the bradycardic and sympatho-inhibitory baroreceptor reflex responses, and reduced the rSNA. PE effectively restored time-domain HRV indexes, the bradycardic and sympatho-inhibitory reflex responses, and the rSNA in chronic nicotine-treated rats. PE was effective in preventing the deterioration of time-domain parameters of HRV, arterial baroreceptor dysfunction, and the rSNA after nicotine treatment.

Diabetes promotes renal sympathetic hyperactivity, autonomic imbalance, and cardiovascular and renal dysfunction. Bilateral renal denervation (BRD) has emerged as a treatment for diabetes; however, the mechanisms that underlie the beneficial effects of BRD are unknown.AIMS:The present study evaluated the effects of BRD on autonomic, cardiovascular, metabolic, and renal function in streptozotocin-diabetic rats.MAIN METHODS:Wistar rats were separated into three experimental groups: control (CTR), diabetic (DM), and diabetic that underwent BRD (DM BRD). BRD was performed two weeks after STZ-diabetes induction, the experiments were performed four weeks after DM induction. This study evaluated sympathetic vasomotor nerve activity in different territories (renal, lumbar and splanchnic), arterial baroreceptor reflex, metabolic and renal function.KEY FINDINGS:BRD significantly reduced glycemia, glycosuria, albuminuria, and SGLT2 gene expression in the kidney in DM rats. Renal sympathetic nerve activity (rSNA) was significantly increased and splanchnic sympathetic nerve activity (sSNA) was significantly decreased in DM rats, without changes in lumbar sympathetic nerve activity (lSNA). BRD was able to normalize sSNA and significantly increase lSNA in DM rats compared to control rats. Additionally, cardiac baroreceptor sensitivity was impaired in DM rats, and BRD significantly improved baroreflex sensitivity.SIGNIFICANCE:Our data suggest that renal nerves play an important role in autonomic, cardiovascular, and renal dysfunction in STZ-DM rats. Thus, sympathetic renal hyperactivity should be considered a possible therapeutic target in diabetic patients.

A classic method to evaluate autonomic dysfunction is through the evaluation of heart rate variability (HRV). HRV provides a series of coefficients, such as Standard Deviation of n-n intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD), which have well-established physiological associations. However, using only electrocardiogram (ECG) signals, it is difficult to identify proper autonomic activity, and the standard techniques are not sensitive and robust enough to distinguish pure autonomic modulation in heart dynamics from cardiac dysfunctions. In this proof-of-concept study we propose the use of Poincaré mapping and Recurrence Quantification Analysis (RQA) to identify and characterize stochasticity and chaoticity dynamics in ECG recordings. By applying these non-linear techniques in the ECG signals recorded from a set of Parkinson’s disease (PD) animal model 6-hydroxydopamine (6-OHDA), we showed that they present less variability in long time epochs and more stochasticity in short-time epochs, in their autonomic dynamics, when compared with those of the sham group. These results suggest that PD animal models present more “rigid heart rate” associated with “trembling ECG” and bradycardia, which are direct expressions of Parkinsonian symptoms. We also compared the RQA factors calculated from the ECG of animal models using four computational ECG signals under different noise and autonomic modulatory conditions, emulating the main ECG features of atrial fibrillation and QT-long syndrome.

Spinal cord neurons contribute to elevated sympathetic vasomotor activity in renovascular hypertension (2K1C), particularly, increased actions of angiotensin II. However, the origin of these spinal angiotensinergic inputs remains unclear. The present study aimed to investigate the role of spinal angiotensin II type 1 receptor (AT1) receptors in the sympathoexcitatory responses evoked by the activation of the rostral ventrolateral medulla (RVLM) in control and 2K1C Goldblatt rats. Hypertension was induced by clipping of the left renal artery. After 6 weeks, a catheter (PE-10) filled with losartan was inserted into the subarachnoid space and advanced to the T10-11 vertebral level in urethane-anesthetized rats. The effects of glutamate microinjection into the RVLM on blood pressure (BP), heart rate (HR), and renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively) were evaluated in the presence or absence of spinal AT1 blockade. Tachycardic, pressor, and renal sympathoexcitatory effects caused by RVLM activation were significantly blunted by losartan in 2K1C rats, but not in control rats. However, no differences were found in the gene expression of angiotensin-converting enzyme, angiotensinogen, and renin in the spinal cord segments between the groups. In conclusion, acute sympathoexcitation induced by RVLM activation is dependent on the spinal AT1 receptor in Goldblatt, but not in control, rats. The involvement of other central cardiovascular nuclei in spinal angiotensinergic actions, as well as the source of angiotensin II, remains to be determined in the Goldblatt model.

Sympathetic vasomotor overactivity is a major feature leading to the cardiovascular dysfunction related to obesity. Considering that the retroperitoneal white adipose tissue (rWAT) is an important fat visceral depot and receives intense sympathetic and afferent innervations, the present study aimed to evaluate the effects evoked by bilateral rWAT denervation in obese rats. Male Wistar rats were fed with HFD for 8 consecutive weeks and rWAT denervation was performed at the 6th week. Arterial pressure, splanchnic and renal sympathetic vasomotor nerve activities were assessed and inflammation and the components of the renin -angiotensin system were evaluated in different white adipose tissue depots. HFD animals presented higher serum levels of leptin and glucose, an increase in arterial pressure and splanchnic sympathetic nerve activity; rWAT denervation, normalized these parameters. Pro-inflammatory cytokines levels were significantly increased, as well as RAAS gene expression in WAT of HFD animals; rWAT denervation significantly attenuated these changes. In conclusion, HFD promotes vasomotor sympathetic overactivation and inflammation with repercussions on the cardiovascular system. In conclusion, the neural communication between WAT and the brain is fundamental to trigger sympathetic vasomotor activation and this pathway is a possible new therapeutic target to treat obesity-associated cardiovascular dysfunction.

Renal sensory activity is centrally integrated within brain nuclei involved in the control of cardiovascular function, suggesting that renal afferents regulate basal and reflex sympathetic vasomotor activity. Evidence has shown that renal deafferentation (DAx) evokes a hypotensive and sympathoinhibitory effect in experimental models of cardiovascular diseases; however, the underlying mechanisms involved in this phenomenon need to be clarified, especially those related to central aspects. We aimed to investigate the role of renal afferents in the control of γ-aminobutyric acid (GABA)ergic inputs to the paraventricular nucleus (PVN) of the hypothalamus in renovascular hypertensive (2K1C) rats and their influence in the regulation of cardiovascular function. Hypertension was induced by clipping the left renal artery. After 4 weeks, renal DAx was performed by exposing the left renal nerve to a 33 mM capsaicin solution for 15 min. After 2 weeks of DAx, microinjection of muscimol into the PVN was performed in order to evaluate the influence of GABAergic activity in the PVN and its contribution to the control of renal sympathetic nerve activity (rSNA) and blood pressure (BP). Muscimol microinjected into the PVN triggered a higher drop in BP and rSNA in the 2K1C rats and renal DAx mitigated these responses. These results suggest that renal afferents are involved in the GABAergic changes found in the PVN of 2K1C rats. Although the functional significance of this phenomenon needs to be clarified, it is reasonable to speculate that GABAergic alterations occur to mitigate microglia activation-induced sympathoexcitation in the PVN of 2K1C rats.

Previous studies have been described changes in brain regions contributing to the sympathetic vasomotor overactivity in Goldblatt hypertension (2K1C). Furthermore, changes in the spinal cord are also involved in the cardiovascular and autonomic dysfunction in renovascular hypertension, as intrathecal (i.t.) administration of Losartan (Los) causes a robust hypotensive/sympathoinhibitory response in 2K1C but not in control rats. The present study evaluated the role of spinal γ-aminobutyric acid (GABA)-ergic inputs in the control of sympathetic vasomotor activity in the 2K1C rats. Hypertension was induced by clipping the renal artery. After six weeks, a catheter (PE-10) was inserted into the subarachnoid space and advanced to the T10-11 vertebral level in urethane-anaesthetized rats. The effects of i.t. injection of bicuculline (Bic) on blood pressure (BP), renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively) were evaluated over 40 consecutive minutes in the presence or absence of spinal AT1 antagonism. I.t. Bic triggered a more intense pressor and sympathoexcitatory response in 2K1C rats, however, these responses were attenuated by previous i.t. Los. No differences in the gene expression of GAD 65 and GABA-A receptors subunits in the spinal cord segments were found. Thus, the sympathoexcitation induced by spinal GABA-A blockade is dependent of local AT1 receptor in 2K1C but not in control rats. Excitatory angiotensinergic inputs to sympathetic preganglionic neurons are tonic controlled by spinal GABAergic actions in Goldblatt hypertension.

Sympathetic nervous system and renin‐angiotensin‐aldosterone system overactivation plays a major role in cardiovascular changes in obesity. The white adipose tissue (WAT) is an essential endocrine organ that synthesizes several biologically active compounds that regulate metabolic homeostasis and contains both sensorial and sympathetic innervation. This study aimed to investigate the effects of retroperitoneal white adipose tissue (rWAT) denervation (DNX) on cardiovascular and renal parameters in obese rats. Animals were treated with a high‐fat diet (HFD) for 8 weeks to induce obesity and underwent surgical DNX procedure at 6 weeks. At the end of the experimental protocol, animals treated with HFD were significantly overweight, whereas the HFD+DNX group had a slightly decrease in body weight. The HFD group presented a discrete increase in baseline mean arterial pressure, which was normalized after DNX. Moreover, DNX improved bradycardic response gain when cardiac baroreflex control was evaluated in the HFD group. No changes were found in renal parameters. However, it was found a significant decrease in circulating angiotensinogen and leptin after rWAT DNX. Therefore, these findings suggest that rWAT innervation has influence on cardiovascular changes found in obesity.Support or Funding InformationCAPES, CNPq and FAPESP

Elevated sympathetic vasomotor activity is a common feature of cardiorenal diseases. Therefore, the sympathetic nervous system is an important therapeutic target, particularly the fibers innervating the kidneys. In fact, renal denervation has been applied clinically and shown promising results in patients with hypertension and chronic kidney disease. However, the underlying mechanisms involved in the cardiorenal protection induced by renal denervation have not yet been fully clarified. This mini-review highlights historical and recent aspects related to the role of renal sensory fibers in the control of cardiorenal function under normal conditions and in experimental models of cardiovascular disease. Results have demonstrated that alterations in renal sensory function participate in the maintenance of elevated sympathetic vasomotor activity and cardiorenal changes; as such, renal sensory fibers may be a potential therapeutic target for the treatment of cardiorenal diseases. Although it has not yet been applied in clinical practice, selective afferent renal denervation may be promising, since such an approach maintains efferent activity and can provide more refined control of renal function compared with total renal denervation. However, more studies are needed to understand the mechanisms by which renal afferents partially contribute to such changes, in addition to the need to evaluate the safety and advantages of the approach for application in the clinical practice.