Blockade of Rostral Ventrolateral Medulla (RVLM) Bombesin Receptor Type 1 Decreases Blood Pressure and Sympathetic Activity in Anesthetized Spontaneously Hypertensive Rats

Pinto, Izabella S.; Mourão, Aline A.; Silva, Elaine F. da; Camargo, Amanda S.; Marques, Stefanne M.; Gomes, Karina Pereira; Fajemiroye, James Oluwagbamigbe; Reis, Ângela Adamski da Silva; Rebelo, Ana Cristina Silva; Ferreira-Neto, Marcos L.; Rosa, Daniel Alves; Freiria-Oliveira, André Henrique; Castro, Carlos H.; Colombari, Eduardo; Colugnati, Diego Basile; Pedrino, Gustavo Rodrigues

doi:10.3389/fphys.2016.00205

Cited by 7 publications

(3 citation statements)

References 48 publications

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“…; Pinto et al . ). AITC evoked relatively similar bradypnoeic breathing responses in conscious WKY and SH rats, regardless of the route of administration.…”

Section: Discussionmentioning

confidence: 97%

Nociceptive pulmonary‐cardiac reflexes are altered in the spontaneously hypertensive rat

Hooper

Stanford

Alencar

et al. 2019

The Journal of Physiology

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Key pointsr We investigated the cardiovascular and respiratory responses of the normotensive Wistar-Kyoto (WKY) rat and the spontaneously hypertensive (SH) rat to inhalation and intravenous injection of the noxious stimuli allyl isothiocyanate (AITC).r AITC inhalation evoked atropine-sensitive bradycardia in conscious WKY rats, and evoked atropine-sensitive bradycardia and atenolol-sensitive tachycardia with premature ventricular contractions (PVCs) in conscious SH rats.r Intravenous injection of AITC evoked bradycardia but no tachycardia/PVCs in conscious SHs, while inhalation and injection of AITC caused similar bradypnoea in conscious SH and WKY rats.r Anaesthesia (inhaled isoflurane) inhibited the cardiac reflexes evoked by inhaled AITC but not injected AITC.r Data indicate the presence of a de novo nociceptive pulmonary-cardiac reflex triggering sympathoexcitation in SH rats, and this reflex is dependent on vagal afferents but is not due to steady state blood pressure or due to remodelling of vagal efferent function.Abstract Inhalation of noxious irritants/pollutants activates airway nociceptive afferents resulting in reflex bradycardia in healthy animals. Nevertheless, noxious pollutants evoke sympathoexcitation (tachycardia, hypertension) in cardiovascular disease patients. We hypothesize that cardiovascular disease alters nociceptive pulmonary-cardiac reflexes. Here, we studied reflex responses to irritants in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive (SH) rats. Inhaled allyl isothiocyanate (AITC) evoked atropine-sensitive bradycardia with atrial-ventricular (AV) block in conscious WKY rats, thus indicating a parasympathetic reflex. Conversely, inhaled AITC in conscious SH rats evoked complex brady-tachycardia J. Shane Hooper completed his BS in biology at the University of South Carolina and attaining a Professional Science Masters in biotechnology at the University of South Florida led him to realize that his scientific career would be in the field of research. He stayed at USF to complete his PhD studying arrhythmia evoked by airway nociceptive reflexes in healthy and cardiovascular diseased rats. He has learned that his true passion is in doing in vivo research and perfecting the required surgical procedures. His biggest challenge and future aspirations are to understand how cardiovascular disease alters neuronal interactions between the lungs and the heart. 3256 J. S. Hooper and others J Physiol 597.13with both AV block and premature ventricular contractions (PVCs). Atropine abolished the bradycardia and AV block, but the atropine-insensitive tachycardia and PVCs were abolished by the β 1 -adrenoceptor antagonist atenolol. The aberrant AITC-evoked reflex in SH rats was not reduced by acute blood pressure reduction by captopril. Surprisingly, intravenous AITC only evoked bradycardia in conscious SH and WKY rats. Furthermore, anaesthesia reduced the cardiac reflexes evoked by inhaled but not injected AITC. Nevertheless, anaesthesia had little effect on AITC-evoked respiratory ...

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“…; Pinto et al . ). AITC evoked relatively similar bradypnoeic breathing responses in conscious WKY and SH rats, regardless of the route of administration.…”

Section: Discussionmentioning

confidence: 97%

Nociceptive pulmonary‐cardiac reflexes are altered in the spontaneously hypertensive rat

Hooper

Stanford

Alencar

et al. 2019

The Journal of Physiology

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“…It is well known that the RVLM plays a key role in regulation of sympathetic out flow [ 24 , 25 ]. The abnormalities of the RVLM in the regulation of sympathetic nerve activity contribute to cardiovascular dysfunction like chronic heart failure and hypertension [ 25 , 26 ]. Previous studies have suggested that HCY plays a role as a neurotransmitter or neuromodulator in the medullary autonomic nuclei [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

The Cardiovascular Effect of Systemic Homocysteine Is Associated with Oxidative Stress in the Rostral Ventrolateral Medulla

Zhong

Zhao²,

et al. 2017

Neural Plasticity

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It has been demonstrated that homocysteine (HCY) is a significant risk factor of hypertension, which is characterized by overactivity of sympathetic tone. Excessive oxidative stress in the rostral ventrolateral medulla (RVLM), a key region for control of sympathetic outflow, contributes to sympathetic hyperactivity in hypertension. Therefore, the goal of the present study is to determine the effect of systemic HCY on production of reactive oxygen species (ROS) in the RVLM. In the rat model of the diet-induced hyperhomocysteinemia (L-methionine, 1 g/kg/day, 8 weeks), we found that the HCY resulted in a significant increase (≈3.7-fold, P < 0.05) in ROS production in the RVLM, which was paralleled with enhanced sympathetic tone and blood pressure (BP). Compared to the vehicle group, levels of BP and basal renal sympathetic nerve activity in the HCY group were significantly (P < 0.05, n = 5) increased by an average of 27 mmHg and 31%, respectively. Furthermore, the rats treated with L-methionine (1 g/kg/day, 8 weeks) showed an upregulation of NADPHase (NOX4) protein expression and a downregulation of superoxide dismutase protein expression in the RVLM. The current data suggest that central oxidative stress induced by systemic HCY plays an important role in hypertension-associated sympathetic overactivity.

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“…Localization of the neurons involved suggests possible different regions of bombesin-like peptide action. Bombesin administered directly into RVLM induces increases in MAP both in normotensive and spontaneously hypertensive rats (SHR), and BIM-23127 reduces MAP and renal sympathetic nerve activity in SHR but not in normal rats [25]. On the other hand, the studies by Lateef et al [26] show an increase in sympathetic nervous system activity, with subsequent pressor and tachycardic effects, after the activation of hypothalamic BB 3 receptors.…”

Section: Discussionmentioning

confidence: 99%

Bombesin-like peptides are able to affect central histamine-induced resuscitating effect in haemorrhage-shocked rats

Jasikowska

Rybus-Kalinowska

Klose

et al. 2020

Ann. Acad. Med. Siles.

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Wstęp:Pobudzenie ośrodkowego układu histaminergicznego wywołuje działanie resuscytacyjne u szczurów we wstrząsie krwotocznym. Skoro podawana dożylnie bombezyna wykazuje podobne działanie, a receptory bombezynowe są obecne w strukturach ośrodkowego układu nerwowego, odpowiedzialnych za regulację czynności układu krążenia, celem pracy było zbadanie wpływu zablokowania receptorów bombezynowych na efekty krążeniowe wynikające z podania do komory bocznej mózgu (icv) histaminy we wstrząsie krwotocznym u szczurów.Materiał i metody:Badania przeprowadzono u szczurów, samców szczepu Wistar w znieczuleniu ogólnym (ketamina 100 mg/kg + ksylazyna 10 mg/kg, dootrzewnowo). Zastosowano model odwracalnego wstrząsu krwotocznego ze średnim ciśnieniem tętniczym (MAP) 30–35 mmHg. Niezwłocznie po zakończeniu krwawienia podawano icv antagonistów receptorów bombezynowych/0,9% roztwór NaCl, a 5 min później tą samą drogą histaminę (50 nmol) bądź 0,9% roztwór NaCl.Wyniki:Utrata krwi prowadziła do obniżenia ciśnienia tętna (PP), częstości rytmu serca (HR) i przepływu krezkowego krwi (MBF). Histamina wywoływała działanie presyjne ze wzrostem PP i MBF. Efekty działania histaminy były częściowo hamowane przez [D-Phe12,Leu14]-bombezynę i BIM 23042, odpowiednio nieselektywnego antagonistę receptorów bombezynowych oraz selektywnego blokera receptorów bombezynowych typu 1 (BB1). W grupach kontrolnych nie stwierdzono wpływu antagonistów receptorów bombezynowych na mierzone parametry układu krążenia.Wnioski:Endogenne peptydy bombezynopodobne, działając poprzez receptory BB1, mogą wpływać na wywoływane przez ośrodkowo działającą histaminę działanie resuscytacyjne we wstrząsie krwotocznym u szczurów.

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Blockade of Rostral Ventrolateral Medulla (RVLM) Bombesin Receptor Type 1 Decreases Blood Pressure and Sympathetic Activity in Anesthetized Spontaneously Hypertensive Rats

Cited by 7 publications

References 48 publications

Nociceptive pulmonary‐cardiac reflexes are altered in the spontaneously hypertensive rat

Nociceptive pulmonary‐cardiac reflexes are altered in the spontaneously hypertensive rat

The Cardiovascular Effect of Systemic Homocysteine Is Associated with Oxidative Stress in the Rostral Ventrolateral Medulla

Bombesin-like peptides are able to affect central histamine-induced resuscitating effect in haemorrhage-shocked rats

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