scholarly journals Neurohumoral Control of Sinoatrial Node Activity and Heart Rate: Insight From Experimental Models and Findings From Humans

2020 ◽  
Vol 11 ◽  
Author(s):  
Eilidh A. MacDonald ◽  
Robert A. Rose ◽  
T. Alexander Quinn
Keyword(s):  
Heart Rate ◽  
Sinoatrial Node ◽  
Experimental Models ◽  
Node Activity ◽  
Neurohumoral Control

scholarly journals Genetic Inhibition of Na + -Ca 2+ Exchanger Current Disables Fight or Flight Sinoatrial Node Activity Without Affecting Resting Heart Rate

2013 ◽  
Vol 112 (2) ◽  
pp. 309-317 ◽  
Author(s):  
Zhan Gao ◽  
Tyler P. Rasmussen ◽  
Yue Li ◽  
William Kutschke ◽  
Olha M. Koval ◽  
...  
Keyword(s):  
Heart Rate ◽  
Sinoatrial Node ◽  
Resting Heart Rate ◽  
Node Activity ◽  
Fight Or Flight

Abstract MP45: Deletion Of The Transient Receptor Vanilloid-1 (TRPV1) Channel In Rats Attenuates 2 Kidney 1 Clip Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Sean D Stocker ◽  
Leon J DeLalio
Keyword(s):  
Heart Rate ◽  
Renovascular Hypertension ◽  
Sensory Nerve ◽  
Experimental Models ◽  
Sensory Nerves ◽  
Male Rats ◽  
Wild Type ◽  
Renal Nerve ◽  
Trpv1 Channels ◽  
Arterial Blood

Renal denervation lowers arterial blood pressure (ABP) in both clinical populations and multiple experimental models of hypertension. This therapeutic effect is partly attributed to the removal of overactive renal sensory nerves that increase sympathetic efferent activity and ABP. Renal sensory nerves highly express TRPV1 channels, and administration of the TRPV1 agonist capsaicin increases renal sensory nerve activity. However, the extent by which TRPV1 channels directly contribute to renal nerve dependent models of hypertension has not been tested. To test this hypothesis, we generated a novel TRPV1 -/- rat using CRISPR/Cas9 and deletion of exon 3. Male and female TRPV1 -/- and wild-type littermates (8-12 weeks) were instrumented with telemetry. At 2 weeks later, renovascular hypertension via renal stenosis was produced by placement of a PTFE cuff (0.16 x 0.22 inches, 1mm long) around the right renal artery. Male TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (99±2 vs 98±3 mmHg, respectively; n=7-9) or heart rate (390±7 vs 400±8 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, mean ABP was significantly lower at Day 28 in male TRPV1 -/- versus wild-type rats (125±8 vs 155±2 mmHg, respectively: P<0.01). Ganglionic blockade with chlorisondamine (2.5mg/kg, sc) at Day 28 produced a smaller fall in mean ABP of male TRPV1 -/- versus wild-type rats (-53±4 vs -86±3 mmHg, respectively; P<0.001). On the other hand, female TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (102±2 vs 104±1 mmHg, respectively; n=6-9) or heart rate (419±8 vs 410±7 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, there were no differences at Day 28 between female TRPV1 -/- versus wild-type rats (117±8 vs 122±6 mmHg, respectively). Moreover, the increase in mean ABP was smaller in females versus males. The ganglionic blocker chlorisondamine produced similar depressor responses in female TRPV1 -/- versus wild-type rats (-64±7 vs -65±7 mmHg, respectively). These findings illustrate a sex difference in renovascular hypertension in rats, but importantly indicate that TRPV1 channels contribute to the established phase of renovascular hypertension in male rats.

Integration of heart rate and sympathetic neural effects on AV conduction

1988 ◽  
Vol 254 (4) ◽  
pp. H651-H657
Author(s):  
J. M. Loeb ◽  
J. M. deTarnowsky
Keyword(s):  
Heart Rate ◽  
Sympathetic Activity ◽  
Sinoatrial Node ◽  
Conduction Time ◽  
Atrial Pacing ◽  
Sympathetic Stimulation ◽  
Sympathetic Activation ◽  
Direct Effects ◽  
Av Node ◽  
Av Conduction

Sympathetic activation increases heart rate (HR) and reduces atrioventricular interval (AVI), whereas atrial pacing alone increases AVI. We sought to differentiate the direct effects of sympathetic activation on atrioventricular (AV) conduction time from the indirect changes associated with concurrent alterations in HR. We recorded electrocardiograms, blood pressure (BP), and intracardiac electrograms from chloralose-anesthetized autonomically decentralized dogs. Beat-by-beat HR and AVI data were collected continuously. Sympathetic stimulation (0.25-2.5 Hz; mean 0.81 Hz) resulted in a HR change of +60 beats/min after 60 s. This tachycardia was associated with a mean decrease in AVI of 22 ms. Computer-driven atrial pacing to reproduce the HR associated with control sympathetic stimulation caused a mean AVI increase of 10 ms. Propranolol (200 micrograms) was then administered via the sinoatrial node artery and sympathetic stimulation repeated. Although HR remained constant, AVI decreased by 14.8 ms. The AVIs associated with an identical HR achieved by two different mechanisms (sympathetic stimulation and atrial pacing) were significantly different. Although removal of the contribution of sympathetically induced HR changes on AV conduction might be expected to result in potentiation of neural effects at the AV node, none was evident. Thus sympathetic activity restricted to the AV node is less effective in influencing AV conduction than the response that occurs when HR changes occur concurrently. Therefore, the opposing actions of HR and sympathetic tone on AV conduction may not be predicted by a simple linear relationship.

scholarly journals β3 Adrenergic Receptors in the Sinoatrial Node for Heart Rate Regulation

2021 ◽  
Vol 16 ◽  
Author(s):  
Shu Nakao ◽  
Kazuki Yanagisawa ◽  
Tomoe Ueyama ◽  
Koji Hasegawa ◽  
Teruhisa Kawamura
Keyword(s):  
Heart Rate ◽  
Adrenergic Receptors ◽  
Sinoatrial Node ◽  
Rate Regulation ◽  
Heart Rate Regulation

scholarly journals Shenxian-Shengmai Oral Liquid Improves Sinoatrial Node Dysfunction through the PKC/NOX-2 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Heng Zhang ◽  
Miao Hao ◽  
Lingkang Li ◽  
Keyan Chen ◽  
Jing Qi ◽  
...  
Keyword(s):  
Heart Rate ◽  
Signaling Pathway ◽  
Sinoatrial Node ◽  
Cardiac Conduction ◽  
Potential Mechanism ◽  
Cardiac Syncope ◽  
Common Causes ◽  
Oral Liquid ◽  
Masson Staining

Sick sinus syndrome (SSS) is one of the common causes of cardiac syncope and sudden death; the occurrence of SSS is associated with the accumulation of ROS in the sinoatrial node (SAN). Shenxian-shengmai (SXSM) is a traditional Chinese medicine available as oral liquid that causes a significant increase in heart rate. The objective of this study is to observe the improvement of SXSM on SAN function in SSS mice and explore its potential mechanism. In the current study, SSS was simulated in mice by inducing SAN dysfunction using a micro-osmotic pump to inject angiotensin II (Ang II). The mouse model with SSS was used to determine the effect of SXSM on SAN function and to explore its potential mechanism. Furthermore, the HL-1 cell line, derived from mouse atrial myocytes, was used to simulate SAN pacemaker cells. Our results indicated that SXSM significantly increased the heart rate of SSS mice by reducing the AngII-induced accumulation of ROS in the SAN and by inhibiting the expression of HDAC4, thereby reducing the loss of HCN4, a critical component of the cardiac conduction system. MASSON staining revealed a reduction of SAN damage in SSS mice that were treated with SXSM compared with controls. In vitro experiments showed that AngII treatment caused an upregulation of the PKC/NOX-2 signaling pathway in HL-1 cells which could be prevented by pretreatment with SXSM. The protective effect of SXSM was attenuated upon treatment with the PCK agonist PMA. In conclusion, SXSM reduced the AngII-induced accumulation of ROS in the SAN through the PKC/NOX2 signaling pathway, improving the functioning of the SAN and preventing the decrease of heart rate in SSS mice.

scholarly journals Phosphorylation and modulation of hyperpolarization-activated HCN4 channels by protein kinase A in the mouse sinoatrial node

2010 ◽  
Vol 136 (3) ◽  
pp. 247-258 ◽  
Author(s):  
Zhandi Liao ◽  
Dean Lockhead ◽  
Eric D. Larson ◽  
Catherine Proenza
Keyword(s):  
Heart Rate ◽  
Protein Kinase ◽  
Cyclic Nucleotide ◽  
Sinoatrial Node ◽  
Voltage Dependence ◽  
C Terminus ◽  
Sympathetic Regulation ◽  
Direct Binding ◽  
End Effectors

The sympathetic nervous system increases heart rate by activating β adrenergic receptors and increasing cAMP levels in myocytes in the sinoatrial node. The molecular basis for this response is not well understood; however, the cardiac funny current (If) is thought to be among the end effectors for cAMP signaling in sinoatrial myocytes. If is produced by hyperpolarization-activated cyclic nucleotide–sensitive (HCN4) channels, which can be potentiated by direct binding of cAMP to a conserved cyclic nucleotide binding domain in the C terminus of the channels. β adrenergic regulation of If in the sinoatrial node is thought to occur via this direct binding mechanism, independent of phosphorylation. Here, we have investigated whether the cAMP-activated protein kinase (PKA) can also regulate sinoatrial HCN4 channels. We found that inhibition of PKA significantly reduced the ability of β adrenergic agonists to shift the voltage dependence of If in isolated sinoatrial myocytes from mice. PKA also shifted the voltage dependence of activation to more positive potentials for heterologously expressed HCN4 channels. In vitro phosphorylation assays and mass spectrometry revealed that PKA can directly phosphorylate at least 13 sites on HCN4, including at least three residues in the N terminus and at least 10 in the C terminus. Functional analysis of truncated and alanine-substituted HCN4 channels identified a PKA regulatory site in the distal C terminus of HCN4, which is required for PKA modulation of If. Collectively, these data show that native and expressed HCN4 channels can be regulated by PKA, and raise the possibility that this mechanism could contribute to sympathetic regulation of heart rate.

scholarly journals RGS4 Regulates Parasympathetic Signaling and Heart Rate Control in the Sinoatrial Node

2008 ◽  
Vol 103 (5) ◽  
pp. 527-535 ◽  
Author(s):  
Carlo Cifelli ◽  
Robert A. Rose ◽  
Hangjun Zhang ◽  
Julia Voigtlaender-Bolz ◽  
Steffen-Sebastian Bolz ◽  
...  
Keyword(s):  
Heart Rate ◽  
Rate Control ◽  
Sinoatrial Node ◽  
Heart Rate Control
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