Role of Orexin-B/Orexin 2 receptor in myocardial protection

2019 ◽  
Vol 133 (7) ◽  
pp. 853-857 ◽  
Author(s):  
Roberta Imperatore ◽  
Luigia Cristino
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Direct Effect ◽  
Myocardial Protection ◽  
Cardiovascular Responses ◽  
Clinical Science ◽  
Clinical Severity ◽  
Dependent Manner ◽  
Protective Function

Abstract Emerging evidence attributes to orexins/hypocretins (ORs) a protective function in the regulation of cardiovascular responses, heart rate, and hypertension. However, little is known about any direct effect of orexins in the heart function. This is of special relevance considering that cardiovascular diseases, including myocardial infarction and heart failure, are one of the major causes of mortality in the world. In the article published in Clinical Science (2018) (vol. 132, 2547–2564), Patel and colleagues investigated the role of orexins in myocardial protection. Intriguingly, they revealed a source of orexin-A (OR-A) and orexin-B (OR-B) in the heart and cardiomyocytes of the rat. More interestingly, these peptides exert a direct effect on the heart rate by acting in an autocrine/paracrine manner on their respective receptors (OXRs). Indeed, OR-B, but not OR-A, by acting through orexin receptor-2 (OX2R), exerts direct cardioprotective effects in heart failure models. OR-B/OX2R signalling enhances myosin light chain (MLC) and troponin-I (TnI) phosphorylation in a dose-dependent manner, leading to an increase in the strength of their twitch contraction. This effect is mediated by extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation, both in the rat myocardial tissue and human heart samples. A negative correlation between OX2R expression and clinical severity of symptoms has been found in patients with heart failure. Thus, in addition to the known central effects of orexins/OX2R, the work of Patel and colleagues (Clinical Science (2018) 132, 2547–2564) reports a direct action of OR-B on the heart rate pinpointing to OX2R as a potential therapeutic target for prevention and treatment of cardiovascular disease.

scholarly journals PROGNOSTIC ROLE OF ATRIAL FIBRILLATION AND HEART RATE CONTROL IN CHRONIC HEART FAILURE PATIENTS

2013 ◽  
Vol 61 (10) ◽  
pp. E735
Author(s):  
Savina Nodari ◽  
Marco Triggiani ◽  
Laura Lupi ◽  
Alessandra Manerba ◽  
Giuseppe Milesi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Heart Rate ◽  
Chronic Heart Failure ◽  
Rate Control ◽  
Heart Rate Control ◽  
Prognostic Role ◽  
Heart Failure Patients

Role of paraventricular and supraoptic nuclei in central cardiovascular regulation in the cat

1980 ◽  
Vol 239 (1) ◽  
pp. R137-R142 ◽  
Author(s):  
J. Ciriello ◽  
F. R. Calaresu
Keyword(s):  
Heart Rate ◽  
Cardiovascular Responses ◽  
Inhibitory Influence ◽  
Sympathetic Nervous Systems ◽  
Aortic Depressor Nerve ◽  
Bilateral Lesions ◽  
Alpha Chloralose ◽  
Supraoptic Nuclei ◽  
Stimulation Of

To investigate the role of the paraventricular (PAH) and supraoptic (SON) nuclei in regulation of the cardiovascular system experiments were done in 26 cats anesthetized with alpha-chloralose, paralyzed, and artificially ventilated. Electrical stimulation of histologically verified sites in the region of the PAH and SON elicited increases in arterial pressure in bilaterally vagotomized animals and increases in heart rate both in spinal (C2) animals and in animals bilaterally vagotomized, In addition, stimulation of either the PAH or SON inhibited the reflex vagal bradycardia elicited by stimulation of the carotid sinus nerve (CSN) and bilateral lesions of these areas increased the magnitude of the response. On the other hand, stimulation and lesions of these hypothalamic regions did not alter the magnitude of the cardiovascular responses to stimulation of the aortic depressor nerve. These results demonstrate that stimulation of the PAH and SON elicit cardiovascular responses due to reciprocal changes in activity of the parasympathetic and sympathetic nervous systems and that these structures maintain a tonic inhibitory influence on the heart rate component of the CSN reflex.

scholarly journals Role of nitric oxide-containing factors in the ventilatory and cardiovascular responses elicited by hypoxic challenge in isoflurane-anesthetized rats

2014 ◽  
Vol 116 (11) ◽  
pp. 1371-1381 ◽  
Author(s):  
James P. Mendoza ◽  
Rachael J. Passafaro ◽  
Santhosh M. Baby ◽  
Alex P. Young ◽  
James N. Bates ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Cardiovascular Responses ◽  
Vital Role ◽  
Initial Increase ◽  
Ventilatory Responses ◽  
Arterial Blood ◽  
Anesthetized Rats ◽  
Before And After

Exposure to hypoxia elicits changes in mean arterial blood pressure (MAP), heart rate, and frequency of breathing (fr). The objective of this study was to determine the role of nitric oxide (NO) in the cardiovascular and ventilatory responses elicited by brief exposures to hypoxia in isoflurane-anesthetized rats. The rats were instrumented to record MAP, heart rate, and fr and then exposed to 90 s episodes of hypoxia (10% O2, 90% N2) before and after injection of vehicle, the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME), or the inactive enantiomer d-NAME (both at 50 μmol/kg iv). Each episode of hypoxia elicited a decrease in MAP, bidirectional changes in heart rate (initial increase and then a decrease), and an increase in fr. These responses were similar before and after injection of vehicle or d-NAME. In contrast, the hypoxia-induced decreases in MAP were attenuated after administration of l-NAME. The initial increases in heart rate during hypoxia were amplified whereas the subsequent decreases in heart rate were attenuated in l-NAME-treated rats. Finally, the hypoxia-induced increases in fr were virtually identical before and after administration of l-NAME. These findings suggest that NO factors play a vital role in the expression of the cardiovascular but not the ventilatory responses elicited by brief episodes of hypoxia in isoflurane-anesthetized rats. Based on existing evidence that NO factors play a vital role in carotid body and central responses to hypoxia in conscious rats, our findings raise the novel possibility that isoflurane blunts this NO-dependent signaling.

Role of ivabradine and heart rate lowering in chronic heart failure: guideline update

2018 ◽  
Vol 16 (7) ◽  
pp. 515-526 ◽  
Author(s):  
Sheryl L Chow ◽  
Robert L. Page ◽  
Christophe Depre
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Chronic Heart Failure

Role of High-Dose Beta-Blockers in Patients with Heart Failure with Preserved Ejection Fraction and Elevated Heart Rate

2018 ◽  
Vol 131 (12) ◽  
pp. 1473-1481 ◽  
Author(s):  
Phillip H. Lam ◽  
Neha Gupta ◽  
Daniel J. Dooley ◽  
Steven Singh ◽  
Prakash Deedwania ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Beta Blockers ◽  
High Dose ◽  
Preserved Ejection Fraction ◽  
Patients With Heart Failure ◽  
Elevated Heart Rate

Effect of pharmacological blockade on cardiovascular responses to voluntary and forced diving in muskrats.

1995 ◽  
Vol 198 (11) ◽  
pp. 2307-2315 ◽  
Author(s):  
P E Signore ◽  
D R Jones
Keyword(s):  
Heart Rate ◽  
Neural Control ◽  
Peripheral Resistance ◽  
Cardiovascular Responses ◽  
Adrenergic Blocker ◽  
Adrenergic Blockers ◽  
Pharmacological Blockade ◽  
Parasympathetic Influences ◽  
Neural Effect

Neural control of free and forced diving bradycardia and peripheral resistance was studied in the muskrat (Ondatra zibethicus) by means of acute pharmacological blockade with the muscarinic blocker atropine, the alpha-adrenergic blocker phentolamine and the beta-adrenergic blockers nadolol and propranolol. Saline injection was used as a control. Heart rate in control animals increased before voluntary dives and dropped markedly as soon as the animals submerged. Heart rate started increasing towards the end of voluntary dives and reached pre-dive values within the first 5 s of recovery. Pre-dive and post-dive tachycardia were reduced in beta-blocked animals, emphasizing the role of the sympathetic system during the preparatory and recovery periods of voluntary dives. Diving bradycardia and the acceleration in heart rate before surfacing were abolished by atropine and unaffected by nadolol, demonstrating the importance of vagal efferent activity during diving. The results after blockade with nadolol suggest that there is an accentuated antagonism between the two branches of the autonomic nervous system during diving, so that parasympathetic influences on the heart predominate. Propranolol-treated muskrats had a higher diving heart rate than saline- and nadolol-treated animals, which may be due to a sedative effect caused by propranolol crossing the blood-brain barrier, a blockade of central catecholaminergic pathways or a peripheral neural effect, due to the anaesthetic properties of propranolol. Phentolamine did not affect diving bradycardia, indicating that diving bradycardia occurs independently of peripheral vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Heart rate variability in severe right or left heart failure: the role of pulmonary hypertension and resistances

2004 ◽  
Vol 6 (2) ◽  
pp. 181-185 ◽  
Author(s):  
Laurent Fauchier ◽  
Dominique Babuty ◽  
Alexandre Melin ◽  
Pierre Bonnet ◽  
Pierre Cosnay ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Pulmonary Hypertension ◽  
Heart Rate Variability ◽  
Left Heart ◽  
Left Heart Failure

scholarly journals The role of heart rate and ivabradine in acute heart failure

2019 ◽  
Vol 89 (3) ◽  
Author(s):  
Edoardo Sciatti ◽  
Enrico Vizzardi ◽  
Ivano Bonadei ◽  
Lucia Dallapellegrina ◽  
Valentina Carubelli
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Healthy Subjects ◽  
Beta Blockers ◽  
Resting Heart Rate ◽  
Powerful Predictor ◽  
Treatment Target ◽  
Reduced Ejection Fraction ◽  
Lowering Drug

Resting heart rate (HR) is considered a powerful predictor of mortality both in healthy subjects and in cardiovascular (CV) patients, including those affected by heart failure (HF). Its reduction below 70 bpm is the treatment target in chronic HF with reduced ejection fraction (HFrEF) when sinus rhythm is present. In acute HF (AHF) HR is usually elevated but its role as risk marker is still unknown. Notably, in unstable patients, beta-blockers can be reduced or stopped, thus enhancing this phenomenon. Moreover, some data in literature suggest that HR reduction during hospitalization or HR at discharge or in the vulnerable phase after it are more predictive of early-term events and may be therapeutic targets. On the other hand, ivabradine is a pure HR-lowering drug with no effects on inotropism. Its role in the AHF setting has been recently investigated and is the object of this review.

Role of vasopressin in the cardiovascular response to hypoxia in the conscious rat

1986 ◽  
Vol 251 (6) ◽  
pp. H1316-H1323 ◽  
Author(s):  
B. R. Walker
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Cardiovascular Response ◽  
Peripheral Resistance ◽  
Cardiovascular Responses ◽  
Hypoxic Exposure ◽  
Conscious Rat ◽  
Time Control ◽  
Hemodynamic Variables

Previous experiments have demonstrated that hypoxia stimulates the release of arginine vasopressin in conscious animals including the rat. The present study was designed to test whether AVP may exert a vasoconstrictor influence during hypoxia at varying levels of CO2. Systemic hemodynamics were assessed in conscious rats for 30 min under hypocapnic hypoxic, isocapnic hypoxic, hypercapnic hypoxic, and room air conditions. Progressive effects on heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were observed with varying CO2 under hypoxic conditions. Hypocapnic hypoxia [arterial PO2 (PaO2) = 32 Torr; arterial PCO2 (PaCO2) = 22 Torr] caused HR and CO to rise and TPR to fall. Isocapnic hypoxia (PaO2 = 36 Torr; PaCO2 = 35 Torr) was associated with no significant changes in HR and CO or TPR, whereas hypercapnic hypoxia (PaO2 = 35 Torr; PaCO2 = 51 Torr) caused HR and CO to fall and TPR to rise. Room air time control experiments were associated with no change in measured hemodynamic variables. To determine the possible role of circulating AVP on these cardiovascular responses, additional experiments were performed where the specific V1-vasopressinergic antagonist d(CH2)5Tyr(Me)AVP (10 micrograms/kg iv) was administered at the midpoint of hypoxic exposure. Antagonist administration had no effect on hypocapnic hypoxic animals or animals breathing room air; however, blood pressure and TPR were significantly reduced by d(CH2)5Tyr(Me)AVP in both isocapnic and hypercapnic hypoxic animals. The heart rate response to hypoxia at the various CO2 levels was unaffected; however, cardiac output and stroke volume were increased after V1-antagonism in the isocapnic and hypercapnic hypoxic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

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