Systemic leukotriene B<sub>4</sub> receptor antagonism lowers arterial blood pressure and improves autonomic function in the spontaneously hypertensive rat

Marvar, Paul J.; Hendy, Emma B; Cruise, Thomas D.; Walas, Dawid; DeCicco, Danielle; Vadigepalli, Rajanikanth; Schwaber, James S.; Waki, Hidefumi; Murphy, David; Paton, Julian F. R.

doi:10.1113/jp272065

Cited by 17 publications

(11 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the changes noted during this pre-hypertension period were dysregulation of pro-fibrotic pathways (e.g., upregulation of enolase-1) and inflammatory pathways (e.g., inhibition of interferons, TLR3 and STAT1) as well as altered mitochondrial function. The authors proposed that these changes support previously reported immune cell infiltration ( Waki et al, 2007 , 2013 ; Xu et al, 2012 ; Marvar et al, 2016 ). The resulting vessel remodeling alters vascular function, increasing cerebrovascular resistance and decreasing CBF, both of which contribute to increased sympathetic nerve activity via the Cushing mechanism, as recently reviewed ( McBryde et al, 2017 ).…”

Section: Vascular Risk Factors and The Nvusupporting

confidence: 76%

Vasculo-Neuronal Coupling and Neurovascular Coupling at the Neurovascular Unit: Impact of Hypertension

et al. 2020

View full text Add to dashboard Cite

Components of the neurovascular unit (NVU) establish dynamic crosstalk that regulates cerebral blood flow and maintain brain homeostasis. Here, we describe accumulating evidence for cellular elements of the NVU contributing to critical physiological processes such as cerebral autoregulation, neurovascular coupling, and vasculoneuronal coupling. We discuss how alterations in the cellular mechanisms governing NVU homeostasis can lead to pathological changes in which vascular endothelial and smooth muscle cell, pericyte and astrocyte function may play a key role. Because hypertension is a modifiable risk factor for stroke and accelerated cognitive decline in aging, we focus on hypertension-associated changes on cerebral arteriole function and structure, and the molecular mechanisms through which these may contribute to cognitive decline. We gather recent emerging evidence concerning cognitive loss in hypertension and the link with vascular dementia and Alzheimer's disease. Collectively, we summarize how vascular dysfunction, chronic hypoperfusion, oxidative stress, and inflammatory processes can uncouple communication at the NVU impairing cerebral perfusion and contributing to neurodegeneration.

show abstract

Section: Vascular Risk Factors and The Nvusupporting

confidence: 76%

Vasculo-Neuronal Coupling and Neurovascular Coupling at the Neurovascular Unit: Impact of Hypertension

et al. 2020

View full text Add to dashboard Cite

show abstract

“…) and, in experimental animal models of CV disease, anti‐inflammatory treatments have been shown to affect autonomic and baroreceptor function (Marvar et al . ). PTSD is associated with higher circulating levels of inflammatory markers (von Kanel et al .…”

Section: Discussionmentioning

confidence: 97%

“…Decreased BRS could be one contributing mechanisms underlying the link between PTSD and cardiovascular disease risk. Chronic inflammation may contribute to blunted BRS in PTSD because several studies have demonstrated that immune dysfunction is present in this population (von Kanel et al 2007;Spitzer et al 2010;Plantinga et al 2013) and, in experimental animal models of CV disease, anti-inflammatory treatments have been shown to affect autonomic and baroreceptor function (Marvar et al 2016). PTSD is associated with higher circulating levels of inflammatory markers (von Kanel et al 2007;Spitzer et al 2010;Plantinga et al 2013) including CRP, IL-4, IL-6 and intercellular adhesion molecule-1, higher brain angiotensin II levels (Matsumura et al 1998;Saavedra et al 2011), and greater arterial stiffness (Walczewska et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Baroreflex dysfunction and augmented sympathetic nerve responses during mental stress in veterans with post‐traumatic stress disorder

Park

Marvar

Liao

et al. 2017

The Journal of Physiology

Self Cite

109

101

View full text Add to dashboard Cite

Key pointsr Patients with post-traumatic stress disorder (PTSD) are at a significantly higher risk of developing hypertension and cardiovascular disease. The mechanisms underlying this increased risk are not known.r Studies have suggested that PTSD patients have an overactive sympathetic nervous system (SNS) that could contribute to cardiovascular risk; however, sympathetic function has not previously been rigorously evaluated in PTSD patients.r Using direct measurements of sympathetic nerve activity and pharmacological manipulation of blood pressure, we show that veterans with PTSD have augmented SNS and haemodynamic reactivity during both combat-related and non-combat related mental stress, impaired sympathetic and cardiovagal baroreflex sensitivity, and increased inflammation.r Identifying the mechanisms contributing to increased cardiovascular (CV) risk in PTSD will pave the way for developing interventions to improve sympathetic function and reduce CV risk in these patients.Abstract Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular (CV) risk. We tested the hypothesis that PTSD patients have augmented sympathetic nervous system (SNS) and haemodynamic reactivity during mental stress, as well as impaired arterial baroreflex sensitivity (BRS). Fourteen otherwise healthy Veterans with combat-related PTSD were compared with 14 matched Controls without PTSD. Muscle sympathetic nerve activity (MSNA), continuous blood pressure (BP) and electrocardiography were measured at baseline, as well as during two types of mental stress: combat-related mental stress using virtual reality combat exposure (VRCE) and non-combat related stress using mental arithmetic (MA). A cold pressor test (CPT) was administered for comparison. BRS was tested using pharmacological manipulation of BP via the Modified Oxford technique at rest and during VRCE. Blood samples were analysed for inflammatory biomarkers. Baseline characteristics, MSNA and haemodynamics were similar between the groups. In PTSD vs. Controls, MSNA (+8.2 ± 1.0 vs. +1.2 ± 1.3 bursts min -1 , P < 0.001) and heart rate responses (+3.2 ± 1.1 vs. −2.3 ± 1.0 beats min -1 , P = 0.003) were significantly augmented during VRCE. Similarly, in PTSD vs. Controls, MSNA (+21.0 ± 2.6 vs. +6.7 ± 1.5 bursts min -1 , P < 0.001) and diastolic BP responses (+6.3 ± 1.0 vs. +3.5 ± 1.0 mmHg, P = 0.011) were significantly augmented during MA but not during CPT (P = not significant). In the PTSD group, sympathetic BRS (-1.2 ± 0.2 vs. -2.0 ± 0.3 burst incidence mmHg and cardiovagal BRS (9.5 ± 1.4 vs. 23.6 ± 4.3 ms mmHg −1 , P = 0.008) were significantly blunted at rest. PTSD patients had significantly higher highly sensitive-C-reactive protein levels compared to Controls (2.1 ± 0.4 vs. 1.0 ± 0.3 mg L −1 , P = 0.047). Augmented SNS and haemodynamic responses to mental stress, blunted BRS and inflammation may contribute to an increased CV risk in PTSD.

show abstract

“…), the baroreflex (Head & Adams, ; Marvar et al . ), the Bezold‐Jarish reflex (Widdop et al . ), and mechano‐ and metabo‐reflexes from skeletal muscle (Leal et al .…”

Section: Discussionmentioning

confidence: 99%

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

Hooper

Stanford

Alencar

et al. 2019

The Journal of Physiology

View full text Add to dashboard Cite

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 ...

show abstract

Systemic leukotriene B₄ receptor antagonism lowers arterial blood pressure and improves autonomic function in the spontaneously hypertensive rat

Abstract: General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms

Cited by 17 publications

References 87 publications

Vasculo-Neuronal Coupling and Neurovascular Coupling at the Neurovascular Unit: Impact of Hypertension

Vasculo-Neuronal Coupling and Neurovascular Coupling at the Neurovascular Unit: Impact of Hypertension

Baroreflex dysfunction and augmented sympathetic nerve responses during mental stress in veterans with post‐traumatic stress disorder

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

Contact Info

Product

Resources

About

Systemic leukotriene B4 receptor antagonism lowers arterial blood pressure and improves autonomic function in the spontaneously hypertensive rat

Abstract: General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms

Cited by 17 publications

References 87 publications

Vasculo-Neuronal Coupling and Neurovascular Coupling at the Neurovascular Unit: Impact of Hypertension

Vasculo-Neuronal Coupling and Neurovascular Coupling at the Neurovascular Unit: Impact of Hypertension

Baroreflex dysfunction and augmented sympathetic nerve responses during mental stress in veterans with post‐traumatic stress disorder

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

Contact Info

Product

Resources

About

Systemic leukotriene B₄ receptor antagonism lowers arterial blood pressure and improves autonomic function in the spontaneously hypertensive rat