Molecular Mechanisms Underlying Renin-Angiotensin-Aldosterone System Mediated Regulation of BK Channels

Zhang, Zhen-Ye; Qian, Lingling; Wang, Ruxing

doi:10.3389/fphys.2017.00698

Cited by 10 publications

(5 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ang-II is the major effector of the RAAS axis, causing systemic vasoconstriction, raising blood pressure, and promoting fluid retention, and it is critical for maintaining fluid balance homeostasis through aldosterone secretion. Despite their high Ang-II levels, POTS patients are paradoxically prone to hypovolemia (37). One explanation would be that POTS patients respond differently to Ang-II.…”

Section: Hypovolemic Potsmentioning

confidence: 99%

Postural Orthostatic Tachycardia Syndrome: Mechanisms and New Therapies

2020

View full text Add to dashboard Cite

Postural orthostatic tachycardia syndrome (POTS) is a clinically heterogeneous disorder with multiple contributing pathophysiologic mechanisms manifesting as symptoms of orthostatic intolerance in the setting of orthostatic tachycardia (increase in heart rate by at least 30 beats per minute upon assuming an upright position) without orthostatic hypotension. The three major pathophysiologic mechanisms include partial autonomic neuropathy, hypovolemia, and hyperadrenergic state. Patients often will exhibit overlapping characteristics from more than one of these mechanisms. The approach to the treatment of POTS centers on treating the underlying pathophysiologic mechanism. Stockings, abdominal binders, and vasoconstrictors are used to enhance venous return in partial neuropathic POTS. Exercise and volume expansion are the main treatment strategies for hypo-volemic POTS. For hyperadrenergic POTS, beta-blockers and avoidance of norepinephrine reuptake inhibitors is important. Attempts should be made to discern which pathophysiologic mechanism(s) may be afflicting patients so that treatment regimens can be individualized.

show abstract

Section: Hypovolemic Potsmentioning

confidence: 99%

Postural Orthostatic Tachycardia Syndrome: Mechanisms and New Therapies

2020

View full text Add to dashboard Cite

show abstract

“…[ 3 ] Abnormal RAAS activity, characterised by inadequate aldosterone secretion by angiotensin II, is the main mechanism of hypovolaemia. [ 13 ] Chronic deconditioning is also associated with hypovolaemia. [ 3 ] However, the reduction of stroke volume in deconditioning is shown to be disproportionate to the degree of hypovolaemia, and reduced myocardial mass also contributes to suboptimal cardiac output in this condition.…”

Section: Pathophysiology Of Potsmentioning

confidence: 99%

Non-invasive Vagus Nerve Simulation in Postural Orthostatic Tachycardia Syndrome

Chakraborty,

Farhat,

Morris

et al. 2023

Arrhythm Electrophysiol Rev

View full text Add to dashboard Cite

Postural orthostatic tachycardia syndrome (POTS) is a chronic debilitating condition of orthostatic intolerance, predominantly affecting young females. Other than postural tachycardia, symptoms of POTS include a spectrum of non-cardiac, systemic and neuropsychiatric features. Despite the availability of widespread pharmacological and non-pharmacological therapeutic options, the management of POTS remains challenging. Exaggerated parasympathetic withdrawal and sympathetic overdrive during postural stress are principal mechanisms of postural tachycardia in POTS. Non-invasive, transcutaneous, vagus nerve stimulation (tVNS) is known to restore sympathovagal balance and is emerging as a novel therapeutic strategy in cardiovascular conditions including arrhythmias and heart failure. Furthermore, tVNS also exerts immunomodulatory and anti-inflammatory effects. This review explores the effects of tVNS on the pathophysiology of POTS and its potential as an alternative non-pharmacological option in this condition.

show abstract

“… 6 , 7 It has four subtypes, with the β1 subtype being abundantly expressed in coronary arterial smooth muscle cells (SMCs). 8 Our previous study demonstrated that BK channel currents account for approximately 65% of the total potassium currents in rat coronary arteries. 9 Considerable evidence suggests that the downregulation of BK-β1 subunit in diabetes is primarily responsible for BK channel dysfunction.…”

Section: Introductionmentioning

confidence: 97%

Advanced glycation end products impair coronary artery BK channels via AMPK/Akt/FBXO32 signaling pathway

Li,

Qian,

et al. 2023

Diabetes and Vascular Disease Research

Self Cite

View full text Add to dashboard Cite

Background: Advanced glycation end products (AGEs) impair vascular physiology in Diabetes mellitus (DM). However, the underlying mechanisms remain unclear. Vascular large conductance calcium-activated potassium (BK) channels play important roles in coronary arterial function. Purpose: Our study aimed to investigate the regulatory role of AGEs in BK channels. Research Design: Using gavage of vehicle (V, normal saline) or aminoguanidine (A) for 8 weeks, normal and diabetic rats were divided into four groups: C+V group, DM+V group, C+A group, and DM+A group. Study Sample: Coronary arteries from different groups of rats and human coronary smooth muscle cells were used in this study. Data Collection and Analysis: Data were presented as mean ± SEM (standard error of mean). Student's t-test was used to compare data between two groups. One-way ANOVA with post-hoc LSD analysis was used to compare data between multiple groups. Results: Compared to the C+V group, vascular contraction induced by iberiotoxin (IBTX), a BK channel inhibitor, was impaired, and BK channel densities decreased in the DM+V group. However, aminoguanidine administration reduced the impairment. Protein expression of BK-β1, phosphorylation of adenosine 5’-monophosphate-activated protein kinase (AMPK), and protein kinase B (PKB or Akt) were down-regulated, while F-box protein 32 (FBXO32) expression increased in the DM+V group and in high glucose (HG) cultured human coronary smooth muscle cells. Treatment with aminoguanidine in vitro and in vivo could reverse the above protein expression. The effect of aminoguanidine on the improvement of BK channel function by inhibiting the generation of AGEs was reversed by adding MK2206 (Akt inhibitor) or Compound C (AMPK inhibitor) in HG conditions in vitro. Conclusions: AGEs aggravate BK channel dysfunction via the AMPK/Akt/FBXO32 signaling pathway.

show abstract

Molecular Mechanisms Underlying Renin-Angiotensin-Aldosterone System Mediated Regulation of BK Channels

Cited by 10 publications

References 88 publications

Postural Orthostatic Tachycardia Syndrome: Mechanisms and New Therapies

Postural Orthostatic Tachycardia Syndrome: Mechanisms and New Therapies

Non-invasive Vagus Nerve Simulation in Postural Orthostatic Tachycardia Syndrome

Advanced glycation end products impair coronary artery BK channels via AMPK/Akt/FBXO32 signaling pathway

Contact Info

Product

Resources

About