scholarly journals Renal Sensory Activity Regulates the γ-Aminobutyric Acidergic Inputs to the Paraventricular Nucleus of the Hypothalamus in Goldblatt Hypertension

2020 ◽  
Vol 11 ◽  
Author(s):  
Maycon I. O. Milanez ◽  
Amanda C. Veiga ◽  
Beatriz S. Martins ◽  
Roberto B. Pontes ◽  
Cassia T. Bergamaschi ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Cardiovascular Function ◽  
Experimental Models ◽  
Left Renal Artery ◽  
Renal Nerve ◽  
Sensory Activity ◽  
Vasomotor Activity ◽  
Underlying Mechanisms ◽  
Gabaergic Activity

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.

Minireview: The involvement of renal afferents in the maintenance of cardiorenal diseases

2020 ◽  
Author(s):  
Amanda C. Veiga ◽  
Maycon I.O. Milanez ◽  
Ruy R. Campos ◽  
Cassia T. Bergamaschi ◽  
Erika E. Nishi
Keyword(s):  
Clinical Practice ◽  
Therapeutic Target ◽  
Renal Denervation ◽  
Experimental Models ◽  
Sensory Function ◽  
Need To Evaluate ◽  
Vasomotor Activity ◽  
Underlying Mechanisms ◽  
Sensory Fibers

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 to 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.

scholarly journals Blocking PAR2 alleviates bladder pain and hyperactivity via TRPA1 signal

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Daihui Chen ◽  
Nian Liu ◽  
Mao Li ◽  
Simin Liang
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Bladder Pain ◽  
Transient Receptor Potential A1 ◽  
Sensory Activity ◽  
Bladder Activity ◽  
Bladder Disorders ◽  
Transient Receptor ◽  
Underlying Mechanisms

AbstractBladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The goals of this study were to examine 1) the effects of blocking proteinase-activated receptor-2 (PAR2) on the exaggerated bladder activity and pain evoked by cystitis and 2) the underlying mechanisms responsible for the role of PAR2 in regulating cystic sensory activity. The protein expression of PAR2 was amplified in rats with cystitis by inducing it with systemic administration of cyclophosphamide (CYP) as compared with control rats. Blocking PAR2 by intrathecal infusion of PAR2 antagonist FSLLRY-NH2 attenuated bladder hyperactivity and pain. In addition, blocking PAR2 attenuated the transient receptor potential A1 (TRPA1) signal pathway, whereas inhibition of the TRPA1 decreased bladder hyperactivity and pain. The data revealed specific signaling pathways leading to CYP-induced bladder hyperactivity and pain, including the activation of PAR2 and TRPA1. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis.

Role of intrarenal α2-adrenoceptors in the renal responses to xylazine in rats

2000 ◽  
Vol 278 (4) ◽  
pp. R1074-R1081 ◽  
Author(s):  
Rubia G. Menegaz ◽  
Daniel R. Kapusta ◽  
Antonio M. Cabral
Keyword(s):  
Urinary Sodium Excretion ◽  
Left Renal Artery ◽  
Renal Nerve ◽  
Excretory Function ◽  
Adrenoceptor Antagonist ◽  
Anesthetized Rats ◽  
Renal Action ◽  
Renal Responses ◽  
Renal Sympathetic

This study examined the contribution of intrarenal α2-adrenoceptor mechanisms to the enhanced urine flow rate (V) and urinary sodium excretion (UNaV) responses in ketamine-xylazine-anesthetized rats. Ten minutes after left renal artery (LRA) injection, the α2-adrenoceptor antagonist yohimbine (5 μg) significantly decreased V from 58 ± 8 to 35 ± 7 μl ⋅ min− 1 ⋅ g kidney wt− 1 and UNaV from 2.8 ± 0.4 to 2.1 ± 0.4 μeq ⋅ min− 1 ⋅ g kidney wt− 1 without altering right kidney function. The renal effects of the LRA injection of yohimbine were completely abolished in chronic bilaterally renal-denervated (RDNX) rats. In RDNX rats, a higher LRA dose of yohimbine (15 μg) significantly reduced left and right kidney V, with no effects on UNaV. In separate bladder-catheterized rats, yohimbine (0.5 mg/kg), 20 min after intravenous injection, significantly decreased V from 63 ± 9 to 13 ± 2 μl ⋅ min− 1 ⋅ g kidney wt− 1 and UNaV from 4.5 ± 0.5 to 1.1 ± 0.1 μeq ⋅ min− 1 ⋅ g kidney wt− 1. In RDNX rats, this dose of yohimbine reduced V and UNaV, but the magnitude was blunted compared with intact rats. In contrast, 0.1 mg/kg iv yohimbine significantly reduced V and UNaV to similar magnitudes in intact and RDNX groups. Together, these findings indicate that intravenous xylazine acts by renal nerve-dependent and -independent mechanisms to enhance renal excretory function in ketamine-anesthetized rats. Because the effects of the LRA dose of yohimbine were abolished in renal-denervated animals, it appears that xylazine has a direct renal action to augment the renal excretion of water and sodium via a presynaptic α2-adrenoceptor pathway that inhibits the release of neurotransmitters from renal sympathetic nerve terminals.

Possible Role of α-Adrenoceptor Subtypes in Acute Migraine Therapy

Cephalalgia ◽  
2003 ◽  
Vol 23 (4) ◽  
pp. 245-257 ◽  
Author(s):  
EW Willems ◽  
LF Valdivia ◽  
CM Villalón ◽  
PR Saxena
Keyword(s):  
Ergot Alkaloids ◽  
Experimental Models ◽  
Adrenoceptor Agonists ◽  
Specific Receptors ◽  
Selective Agonists ◽  
The Common ◽  
Underlying Mechanisms ◽  
Carotid Circulation ◽  
Established Role

Even though the underlying mechanisms for the pathophysiology of migraine attacks are not completely understood, little doubt exists that the headache phase is explained by dilatation of cranial, extracerebral blood vessels. In this context, experimental models predictive for anti-migraine activity have shown that both triptans and ergot alkaloids, which abort migraine headache, produce vasoconstriction within the carotid circulation of different species. In contrast to the well-established role of serotonin (5-hydroxytryptamine; 5-HT) 5-HT1B receptors in the common carotid vascular bed, the role of α-adrenoceptors and their subtypes has been examined only relatively recently. Using experimental animal models and α1- and α2-adrenoceptor agonists (phenylephrine and BHT933, respectively) and antagonists (prazosin and rauwolscine, respectively), it was shown that activation of either receptor produces a cranioselective vasoconstriction. Subsequently, investigations employing relatively selective antagonists at α1- (α1A, α1B, α1D) and α2- (α2A, α2B, α2C) adrenoceptor subtypes revealed that specific receptors mediate the carotid haemodynamic responses in these animals. From these observations, together with the potential limited role of α1B-and α2C-adrenoceptors in the regulation of systemic haemodynamic responses, it is suggested that selective agonists at these receptors may provide a promising novel avenue for the development of acute anti-migraine drugs.

scholarly journals Regulation of sympathetic vasomotor activity by the hypothalamic paraventricular nucleus in normotensive and hypertensive states

2018 ◽  
Vol 315 (5) ◽  
pp. H1200-H1214 ◽  
Author(s):  
Roger A. Dampney ◽  
Lisete C. Michelini ◽  
De-Pei Li ◽  
Hui-Lin Pan
Keyword(s):  
Paraventricular Nucleus ◽  
Molecular Mechanisms ◽  
Spontaneously Hypertensive Rat ◽  
Hypothalamic Paraventricular Nucleus ◽  
Sympathetic Outflow ◽  
Spontaneously Hypertensive ◽  
Acute Hypotension ◽  
Vasomotor Activity ◽  
Spontaneously Hypertensive Rat Model

The hypothalamic paraventricular nucleus (PVN) is a unique and important brain region involved in the control of cardiovascular, neuroendocrine, and other physiological functions pertinent to homeostasis. The PVN is a major source of excitatory drive to the spinal sympathetic outflow via both direct and indirect projections. In this review, we discuss the role of the PVN in the regulation of sympathetic output in normal physiological conditions and in hypertension. In normal healthy animals, the PVN presympathetic neurons do not appear to have a major role in sustaining resting sympathetic vasomotor activity or in regulating sympathetic responses to short-term homeostatic challenges such as acute hypotension or hypoxia. Their role is, however, much more significant during longer-term challenges, such as sustained water deprivation, chronic intermittent hypoxia, and pregnancy. The PVN also appears to have a major role in generating the increased sympathetic vasomotor activity that is characteristic of multiple forms of hypertension. Recent studies in the spontaneously hypertensive rat model have shown that impaired inhibitory and enhanced excitatory synaptic inputs to PVN presympathetic neurons are the basis for the heightened sympathetic outflow in hypertension. We discuss the molecular mechanisms underlying the presynaptic and postsynaptic alterations in GABAergic and glutamatergic inputs to PVN presympathetic neurons in hypertension. In addition, we discuss the ability of exercise training to correct sympathetic hyperactivity by restoring blood-brain barrier integrity, reducing angiotensin II availability, and decreasing oxidative stress and inflammation in the PVN.

scholarly journals The Role of RSV Infection in Asthma Initiation and Progression: Findings in a Mouse Model

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Junyan Han ◽  
Katsuyuki Takeda ◽  
Erwin W. Gelfand
Keyword(s):  
Experimental Models ◽  
Valuable Insight ◽  
Recurrent Wheezing ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Underlying Mechanisms ◽  
Infancy And Early Childhood ◽  
Severe Pulmonary Disease ◽  
Insight Into

Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract diseases (bronchiolitis and pneumonia) during infancy and early childhood. There is increasing evidence which indicates that severe pulmonary disease caused by RSV infection in infancy is associated with recurrent wheezing and development of asthma later in childhood. However, the underlying mechanisms linking RSV infection to persistent airway hyperresponsiveness and dysfunction are not fully defined. To study these processes in ways which are not available in humans, animal models have been established and have provided valuable insight into the pathophysiology of RSV-induced disease. In this paper, we discuss experimental models of RSV infection in mice and highlight a new investigative approach in which mice are initially infected as neonates and then reinfected later in life. The findings shed light on the mechanisms underlying the association between early severe RSV infection and development of asthma later in childhood.

Response Interference as a Mechanism Underlying Implicit Measures

2008 ◽  
Vol 24 (4) ◽  
pp. 218-225 ◽  
Author(s):  
Bertram Gawronski ◽  
Roland Deutsch ◽  
Etienne P. LeBel ◽  
Kurt R. Peters
Keyword(s):  
Task Performance ◽  
Psychological Research ◽  
Implicit Measures ◽  
Mediation Model ◽  
Response Interference ◽  
Relevant Evidence ◽  
Moderated Mediation Model ◽  
Stimulus Features ◽  
Underlying Mechanisms

Over the last decade, implicit measures of mental associations (e.g., Implicit Association Test, sequential priming) have become increasingly popular in many areas of psychological research. Even though successful applications provide preliminary support for the validity of these measures, their underlying mechanisms are still controversial. The present article addresses the role of a particular mechanism that is hypothesized to mediate the influence of activated associations on task performance in many implicit measures: response interference (RI). Based on a review of relevant evidence, we argue that RI effects in implicit measures depend on participants’ attention to association-relevant stimulus features, which in turn can influence the reliability and the construct validity of these measures. Drawing on a moderated-mediation model (MMM) of task performance in RI paradigms, we provide several suggestions on how to address these problems in research using implicit measures.

The More You Say, the Less They Hear

2015 ◽  
Vol 27 (4) ◽  
pp. 159-169 ◽  
Author(s):  
Elsbeth D. Asbeek Brusse ◽  
Marieke L. Fransen ◽  
Edith G. Smit
Keyword(s):  
Hearing Protection ◽  
Entertainment Education ◽  
Mediating Role ◽  
Attitude Measures ◽  
Underlying Mechanisms

Abstract. This study examined the effects of disclosure messages in entertainment-education (E-E) on attitudes toward hearing protection and attitude toward the source. In addition, the (mediating) role of the underlying mechanisms (i.e., transportation, identification, and counterarguing) was studied. In an experiment (N = 336), three different disclosure messages were compared with a no-disclosure condition. The results show that more explicit disclosure messages negatively affect transportation and identification and stimulate the generation of counterarguments. In addition, the more explicit disclosure messages affect both attitude measures via two of these processes (i.e., transportation and counterarguing). Less explicit disclosure messages do not have this effect. Implications of the findings are discussed.

Autophagy Modulators and Neuroinflammation

2020 ◽  
Vol 27 (6) ◽  
pp. 955-982 ◽  
Author(s):  
Kyoung Sang Cho ◽  
Jang Ho Lee ◽  
Jeiwon Cho ◽  
Guang-Ho Cha ◽  
Gyun Jee Song
Keyword(s):  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Mammalian Cells ◽  
Critical Role ◽  
Therapeutic Agents ◽  
Mechanisms Of Action ◽  
Scientific Interest ◽  
Therapeutic Tools ◽  
Underlying Mechanisms

Background: Neuroinflammation plays a critical role in the development and progression of various neurological disorders. Therefore, various studies have focused on the development of neuroinflammation inhibitors as potential therapeutic tools. Recently, the involvement of autophagy in the regulation of neuroinflammation has drawn substantial scientific interest, and a growing number of studies support the role of impaired autophagy in the pathogenesis of common neurodegenerative disorders. Objective: The purpose of this article is to review recent research on the role of autophagy in controlling neuroinflammation. We focus on studies employing both mammalian cells and animal models to evaluate the ability of different autophagic modulators to regulate neuroinflammation. Methods: We have mostly reviewed recent studies reporting anti-neuroinflammatory properties of autophagy. We also briefly discussed a few studies showing that autophagy modulators activate neuroinflammation in certain conditions. Results: Recent studies report neuroprotective as well as anti-neuroinflammatory effects of autophagic modulators. We discuss the possible underlying mechanisms of action of these drugs and their potential limitations as therapeutic agents against neurological disorders. Conclusion: Autophagy activators are promising compounds for the treatment of neurological disorders involving neuroinflammation.

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