Modulation of noradrenaline release through presynaptic α2-adrenoceptors in congestive heart failure

Minatoguchi, Shinya; Ito, Hiroyasu; Ishimura, Koji; Watanabe, Hiroko; Imai, Yoko; Koshiji, Masatoshi; Asano, Kiyoji; Hirakawa, Senri; Fujiwara, Hisayoshi

doi:10.1016/0002-8703(95)90360-7

Cited by 21 publications

(8 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the existence of presynaptic α 2 AR inhibiting noradrenaline release have been directly demonstrated ex vivo in isolated human right atria (33,34) and indirectly in vivo by systemic and intracoronary application of phentolamine (35,36) that caused a marked increase in plasma noradrenaline levels. In this context, it is interesting to note that phentolamine effects on plasma noradrenaline levels were much more pronounced in patients with heart failure (who have increased sympathetic activity, see below) than in healthy subjects.…”

Section: α 2 -Adrenoceptorsmentioning

confidence: 98%

Cardiac Adrenoceptors: Physiological and Pathophysiological Relevance

Brodde¹,

Bruck²,

Leineweber³

2006

J Pharmacol Sci

211

161

View full text Add to dashboard Cite

Abstract. At present, nine adrenoceptor (AR) subtypes have been identified: α 1A -, α 1B -, α 1D -, α 2A -, α 2B -, α 2C -, β 1 -, β 2 -, and β 3 AR. In the human heart, β 1 -and β 2 AR are the most powerful physiologic mechanism to acutely increase cardiac performance. Changes in βAR play an important role in chronic heart failure (CHF). Thus, due to increased sympathetic activity in CHF, βAR are chronically (over)stimulated, and that results in β 1 AR desensitization and alterations of down-stream mechanisms. However, several questions remain open: What is the role of β 2 AR in CHF? What is the role of increases in cardiac G i -protein in CHF? Do increases in G-protein-coupled receptor kinase (GRK)s play a role in CHF? Does βAR-blocker treatment cause its beneficial effects in CHF, at least partly, by reducing GRK-activity? In this review these aspects of cardiac AR pharmacology in CHF are discussed. In addition, new insights into the functional importance of β 1 -and β 2 AR gene polymorphisms are discussed. At present it seems that for cardiovascular diseases, βAR polymorphisms do not play a role as disease-causing genes; however, they might be risk factors, might modify disease, and / or might influence progression of disease. Furthermore, βAR polymorphisms might influence drug responses. Thus, evidence has accumulated that a β 1 AR polymorphism (the Arg389Gly β 1 AR) may affect the response to βAR-blocker treatment.

show abstract

Section: α 2 -Adrenoceptorsmentioning

confidence: 98%

Cardiac Adrenoceptors: Physiological and Pathophysiological Relevance

Brodde¹,

Bruck²,

Leineweber³

2006

J Pharmacol Sci

211

161

View full text Add to dashboard Cite

show abstract

“…α 2 -AR agonists are widely recognized to inhibit stimulation-evoked release of norepinephrine and epinephrine from presynaptic adrenergic nerve terminals 18) and the adrenal medulla. 19) During the progression of congestive heart failure, negative-feedback inhibition through presynaptic α 2 -AR is potentiated, which attenuates excessive norepinephrine release in patients 28) and in mice exposed to pressure overload. 29) Consistent with these findings, sustained (30 minutes) IMO did not increase norepinephrine secretion, possibly reflecting endogenous α 2 -AR-mediated feedback inhibition ( Figure 4B).…”

Section: Discussionmentioning

confidence: 99%

Immobilization Stress With <i>α</i><sub>2</sub>-Adrenergic Stimulation Induces Regional and Transient Reduction of Cardiac Contraction Through Gi Coupling in Rats

et al. 2015

View full text Add to dashboard Cite

SummaryStress cardiomyopathy is characterized by transient apical hypokinesia related to catecholamine overflow. Recently, excessive epinephrine administration was shown to recapitulate stress cardiomyopathy through β 2 -adrenoceptor (AR)-inhibitory G protein (Gi) coupling in rats. We aimed to study whether α 2 -AR and Gi affect cardiac contraction in rats in which emotional stress was evoked using immobilization (IMO). Echocardiography results showed that when male rats were exposed to IMO for 30 minutes and then injected with the α 2 -AR agonist xylazine (Xy), ejection fraction and the movement of the anterior wall (AW) were suppressed, maximally at 5 minutes post-injection, whereas posterior wall (PW) movement was preserved. At the same time points, the phosphorylation of Ser282 in myosin-binding protein-C (MyBP-C-Ser282) was higher in the PW than in the AW. Pretreatment with the Gi inhibitor pertussis toxin (PTX) reversed the low contractility and MyBP-C-Ser282 phosphorylation in the AW, but induced lethal heart failure in 3 out of 11 rats. Moreover, at 5 minutes after Xy injection following 30 minutes of IMO, serum epinephrine levels were increased. Thus, in rats exposed to psychological stress, α 2 -AR stimulation triggered transient hypo-contractility and MyBP-C-Ser282 hypo-phosphorylation in the AW, in association with an epinephrine surge. PTX treatment reversed the AW hypo-contractility and MyBP-C hypo-phosphorylation, but induced acute heart failure. These findings suggest α 2 -AR/Gi-dependent signaling attenuates MyBP-C phosphorylation and contractility in the AW through an epinephrine surge in rats subjected to IMO and α 2 -AR stimulation. This model can recapitulate stress cardiomyopathy and thereby deepen our understanding of regional cardiac hypo-contractility and prosurvival mechanisms. Studies on psychological stress conducted using immobilization (IMO) in rats demonstrated the activation of the hypothalamo-pituitary-adrenocortical and sympatho-adrenomedullary axes. [4][5][6] This model served to establish the fight-andflight doctrine of Hans Selye 7) and has contributed to studies on cardiovascular responses to emotional stress. We reported that IMO induces the expression of cardiac immediate-early genes through α-and β-adrenoceptors (ARs) in rats.8) We also showed that whereas IMO induced enhanced gap-junction (GJ) coupling through α-AR, it triggered lethal ventricular arrhythmias when GJ was inhibited. 9,10)

show abstract

“…Impaired α 2C AR-G protein coupling results in altered functions in three downstream signaling pathways; the adenylyl cyclase, inositol phosphate, and mitogen-activated protein (MAP) kinase [24]. The loss of normal synaptic autoinhibitory feedback caused by this genetic variation leads to enhanced presynaptic release of NE [25,26].…”

Section: Functional Properties Of Adrenore-ceptorsmentioning

confidence: 99%

Pharmacogenomics of Adrenergic Receptors; from Hypertension to Heart Failure

Nonen¹,

Azuma²,

Fujio³

2010

TOHYPERJ

View full text Add to dashboard Cite

Cardiovascular medicine is a leading area of pharmacogenomics (PGx). A number of PGx studies have linked genetic polymorphisms to patients' response to the drugs in the pharmacotherapy against cardiovascular diseases. Among them, PGx of adrenoceptors is one of the most important fields, because adrenergic networks play important roles in cardiovascular systems. The excess of adrenergic stimuli result in cardiovascular disorders, such as hypertension and heart failure (HF). One of the aims of PGx studies of adrenoreceptors is the personalization of β-blocker therapy. In this review, we have described biological and clinical impacts on genetic variants of adrenoreceptors, some of which have showed clear association with the reduction in heart rate and blood pressure in response to β-blockers. Beyond anti-hypertension therapy, PGx of adrenoreceptors would contribute to the individualization of pharmacotherapy against HF.

show abstract

Modulation of noradrenaline release through presynaptic α2-adrenoceptors in congestive heart failure

Cited by 21 publications

References 19 publications

Cardiac Adrenoceptors: Physiological and Pathophysiological Relevance

Cardiac Adrenoceptors: Physiological and Pathophysiological Relevance

Immobilization Stress With <i>α</i><sub>2</sub>-Adrenergic Stimulation Induces Regional and Transient Reduction of Cardiac Contraction Through Gi Coupling in Rats

Pharmacogenomics of Adrenergic Receptors; from Hypertension to Heart Failure

Contact Info

Product

Resources

About