Superoxide anions modulate the performance of apelin in the paraventricular nucleus on sympathetic activity and blood pressure in spontaneously hypertensive rats

Santos

et al. 2020

Sci Rep

Mechanisms involved in the acute responses to renal denervation (RDN) have yet to be fully understood. We assessed urinary volume, autonomic control and aorta vascular reactivity after acute RDN. Male normotensive Wistar rats and spontaneously hypertensive rats (SHR) were divided into normotensive + RDN (ND) or sham surgery (NS), and hypertensive + RDN (HD) or sham surgery (HS). Metabolic parameters and hemodynamic measurements were recorded 72h and 4 days after intervention, respectively. Aortic rings were studied 7 days post RDN in an isometric myograph. Concentration–response curves to phenylephrine, sodium nitroprusside and acetylcholine (10–10–10−5 M) were performed. Two-way ANOVA was used for group comparisons and differences reported when p < 0.05. Results are presented as mean ± SEM. Urinary volume was 112% higher in HD vs. HS (HS = 14.94 ± 2.5 mL; HD = 31.69 ± 2.2 mL) and remained unchanged in normotensive rats. Systolic BP was lower in HD rats (HS = 201 ± 12 vs. HD = 172 ± 3 mmHg) without changes in normotensive group. HD group showed increased HF and LF modulation (HS = 5.8 ± 0.7 ms2vs. HD = 13.4 ± 1.4 ms2; HS = 3.5 ± 0.7 ms2vs. HD = 10.5 ± 1.7 ms2, respectively). RDN normalized vascular reactivity in HD rats and increased phenylephrine response in ND rats. Acute fall in BP induced by RDN is associated with increased urinary volume, which in turn may also have contributed to functional changes of the aorta.

Section: Discussionsupporting

confidence: 62%

Acute renal denervation normalizes aortic function and decreases blood pressure in spontaneously hypertensive rats

Santos

et al. 2020

Sci Rep

“…We observed a similar relationship in our previous study, whereas others reported that ICV administration of APLN‐13 to Wistar rats caused an increase in HR 9,10 . In addition, other researchers have shown that centrally administered APLN‐13 may increase HR if it acts on the pre‐sympathetic neurons located directly in the rostral ventrolateral medulla (RVLM) or the PVN 14,23,24 . In contrast, if the above process does not occur, then the heart rate is regulated by the parasympathetic system, which is the dominant pulse regulator.…”

Section: Discussionsupporting

confidence: 87%

Central interaction between the apelinergic and vasopressinergic systems in the regulation of the haemodynamic parameters in rats maintained on a high‐fat diet

Wojno

Czarzasta

Puchalska

et al. 2020

Clin Exp Pharma Physio

A high‐fat diet can affect the central activity of the apelinergic and vasopressinergic systems, which can have a significant impact on cardiovascular regulation. The aim of the study was to investigate the role of the central interaction between apelin and vasopressin in the regulation of the cardiovascular system in Sprague Dawley rats maintained on a normal‐fat diet (NFD) or on a high‐fat diet (HFD). The animals were instrumented with a cannula implanted into the left cerebral ventricle for intracerebroventricular (ICV) infusions of saline (0.9% NaCl), apelin‐13 (APLN‐13), V1a receptor antagonist (V1aRANT) APJ receptor antagonist (F13A), vasopressin (AVP); and with a catheter placed within the femoral artery for mean arterial blood pressure and heart rate monitoring. Blood, the hypothalamus and the medulla oblongata were collected for biochemical analysis. The hypertensive effect of APLN‐13 was blocked by a prior ICV infusion of V1aRANT, only in the NFD rats. However, the hypertensive effect of AVP was blocked by the prior ICV infusion of F13A in both the NFD and HFD rats. A HFD caused an increase in the protein level of APJ and V1a receptors, both in the hypothalamus and the medulla oblongata. This study confirms the presence of an interaction between both peptides in the central regulation of the cardiovascular system in rats on a NFD or a HFD.

“…ELA is reported to be an endogenous ligand for apelin receptor (APJ) and regulates fluid homeostasis by binding to APJ in kidney 26 . And APJ has been found involved in the regulation of NADPH oxidase and ROS production 36 , 37 . Thus, we examined whether ELA was dependent on APJ to inhibit NADPH oxidase/ROS/NLRP3 inflammasome pathway in the DOCA/salt-treated kidneys.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, it is known that the regulatory effects of apelin on oxidative stress are conducted by binding to its receptor APJ in most experimental conditions 37,46,47 . As another endogenous ligand, it is still unclear whether ELA is dependent on APJ to suppress DOCA/salt-induced NADPH oxidase/ROS/NLRP3 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, there is increasing evidence proving that apelin-13 induces cardiac hypertrophy by increasing the production of ROS and the expression levels of NADPH oxidases in vivo and in vitro 45 – 47 . In addition, apelin/APJ in paraventricular nucleus is found to induce long-term high BP and renal sympathetic nerve activity via increasing oxidative stress 37 , 48 . Thus, there is no identical conclusion on the association of apelin/APJ with oxidative stress and inflammation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

ELABELA attenuates deoxycorticosterone acetate/salt-induced hypertension and renal injury by inhibition of NADPH oxidase/ROS/NLRP3 inflammasome pathway

Chen

Liu

et al. 2020

Cell Death Dis

ELABELA (ELA), a 32-residue hormone peptide abundantly expressed in adult kidneys, has been identified as a novel endogenous ligand for APJ/Apelin receptor. The aim of this study was to investigate the role of ELA in deoxycorticosterone acetate (DOCA)/salt-induced hypertension and further explore the underlying mechanism. In DOCA/salt-treated rats, the mRNA level of ELA greatly decreased in the renal medulla. Next, overexpression of ELA in the kidney was found to attenuate DOCA/salt-induced hypertension and renal injury, including lower blood pressure, reversed glomerular morphological damage, decreased blood urea nitrogen (BUN), and blocked the accumulation of fibrotic markers. Mechanistically, ELA overexpression inhibited renal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and subsequent reactive oxygen species (ROS) production, thus resulted in the blockade of formation and activation of Nod-like receptor protein 3 (NLRP3) inflammasome. The inhibitory effects of ELA on Aldosterone-stimulated NADPH oxidase/ROS/NLRP3 inflammasome pathway were confirmed in the human renal tubular cells. Furthermore, our in vivo and in vitro results showed that the deficiency of the apelin receptor APJ did not influence the antihypertensive effect and blockage to NADPH oxidase/ROS/NLRP3 pathway of ELA. Moreover, in heterozygous ELA knockout mice (ELA+/−), the ELA deficiency remarkably accelerated the onset of DOCA/salt-induced hypertension. Our data demonstrate that ELA prevents DOCA/salt-induced hypertension by inhibiting NADPH oxidase/ROS/NLRP3 pathway in the kidney, which is APJ independent. Pharmacological targeting of ELA may serve as a novel therapeutic strategy for the treatment of hypertensive kidney disease.