The rational use of β‐adrenoceptor blockers in the treatment of heart failure. The changing face of an old therapy

Squire, Iain B.; Barnett, David

doi:10.1046/j.1365-2125.2000.00112.x

Cited by 22 publications

(6 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, carvedilol reduces plasma noradrenaline concentration, whereas another β ‐blocker, atenolol, has no such effect ( Herman et al , 2003 ). The question then arises of why substances that reduce norepinephrine release like carvedilol ( Gilbert et al , 1996 ; Herman et al , 2003 ), downregulate (metoprolol) and block the β ‐adrenergic receptor, increase systolic function of the heart (Squire & Barnett, 2000). Clearly, the immediate effect of β ‐blockers is a reduction in cardiac inotropy and the increase in ejection fraction is seen only after several weeks of treatment ( Metra et al , 2000 ).…”

Section: Discussionmentioning

confidence: 99%

Plasma membrane‐associated nucleoside diphosphate kinase (nm23) in the heart is regulated by β‐adrenergic signaling

Lutz¹,

Mura²,

Hippe³

et al. 2003

British J Pharmacology

View full text Add to dashboard Cite

1 A receptor-independent activation of heterotrimeric G proteins by plasma membrane-associated nucleoside diphosphate kinase (NDPK) has been demonstrated in vivo, and elevated levels of NDPK were found in purified sarcolemmal membranes of patients with end-stage heart failure. 2 Among 22 consecutive patients with chronic heart failure who underwent cardiac transplantation, those treated with a b-blocker (n ¼ 8) had a 65% lower NDPK content and activity in the cardiac sarcolemma, compared to patients with similar base line characteristics who had no b-blocker therapy (n ¼ 14). 3 The lower NDPK was associated with a reduced NDPK-dependent, G i -mediated inhibition of adenylyl cyclase activity, as assessed by in vitro measurement of adenylyl cyclase activity in the presence of GDP or its kinase-resistant analog guanosine 5 0 -O-(2-thio)diphosphate (GDPbS). 4 We further tested whether treatment with a b-adrenergic agonist would induce an increase in sarcolemmal NDPK. Rats treated with isoproterenol developed myocardial hypertrophy, and NDPK in the sarcolemma rose by 60% during 14 days of treatment. The b-blocker propranolol prevented both effects. When hypertrophy was induced with thyroid hormone, NDPK did not increase. 5 In conclusion, chronic activation of b-adrenergic receptors increases the binding of NDPK to cardiac sarcolemma, where it may activate heterotrimeric G proteins.

show abstract

Section: Discussionmentioning

confidence: 99%

Plasma membrane‐associated nucleoside diphosphate kinase (nm23) in the heart is regulated by β‐adrenergic signaling

Lutz¹,

Mura²,

Hippe³

et al. 2003

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…In most cases, a multiple drug regimen is applied for conditions such as chronic heart failure, where patients are treated with diuretics for removal of surplus liquid, ACE inhibitors and/or AT 1 receptor antagonists to cause peripheral vasodilation, digoxin as positive inotropic agent, antithrombotics, antiarrhythmics, anticoagulants, and hypolipidemic drugs. In addition, the aldosterone receptor antagonists, spironolactone and eplerenone, and β‐adrenoceptor antagonists such as metoprolol, bisaprolol, carvedilol, and recently, nebivolol have been found to enhance survival in patients suffering from heart failure [295–297]. Standard heart frequency therapy with β‐adrenoceptor antagonists, digoxin, and thiazide diuretics may worsen sexual dysfunction owing to medication side effects, but evidence regarding the effect on erectile function of most of these drugs is sparse [270].…”

Section: Drugs Causing Edmentioning

confidence: 99%

Anatomy, Physiology, and Pathophysiology of Erectile Dysfunction

Gratzke

Angulo

Chitaley

et al. 2010

The Journal of Sexual Medicine

364

342

View full text Add to dashboard Cite

Introduction Significant scientific advances during the past 3 decades have deepened our understanding of the physiology and pathophysiology of penile erection. A critical evaluation of the current state of knowledge is essential to provide perspective for future research and development of new therapies. Aim To develop an evidence-based, state-of-the-art consensus report on the anatomy, physiology, and pathophysiology of erectile dysfunction (ED). Methods Consensus process over a period of 16 months, representing the opinions of 12 experts from seven countries. Main Outcome Measure Expert opinion was based on the grading of scientific and evidence-based medical literature, internal committee discussion, public presentation, and debate. Results ED occurs from multifaceted, complex mechanisms that can involve disruptions in neural, vascular, and hormonal signaling. Research on central neural regulation of penile erection is progressing rapidly with the identification of key neurotransmitters and the association of neural structures with both spinal and supraspinal pathways that regulate sexual function. In parallel to advances in cardiovascular physiology, the most extensive efforts in the physiology of penile erection have focused on elucidating mechanisms that regulate the functions of the endothelium and vascular smooth muscle of the corpus cavernosum. Major health concerns such as atherosclerosis, hyperlipidemia, hypertension, diabetes, and metabolic syndrome (MetS) have become well integrated into the investigation of ED. Conclusions Despite the efficacy of current therapies, they remain insufficient to address growing patient populations, such as those with diabetes and MetS. In addition, increasing awareness of the adverse side effects of commonly prescribed medications on sexual function provides a rationale for developing new treatment strategies that minimize the likelihood of causing sexual dysfunction. Many basic questions with regard to erectile function remain unanswered and further laboratory and clinical studies are necessary.

show abstract

“…chronic heart failure (CHF) in humans, AC/cAMP/PKA/Ca 2+ signaling progressively increases as the degree of heart failure progresses, leading to cardiac inflammation, mediated in part, by cyclic-AMP-induced up-regulation of renin-angiotensin system (RAS) signaling. Standard therapies for CHF include β-adrenoreceptor blockers and RAS inhibitors, 6, 7 which although effective, are suboptimal in amelioration of heart failure progression.…”

Section: Introductionmentioning

confidence: 99%

A Remarkable Adaptive Paradigm Of Heart Performance And Protection Emerges In Response To The Constitutive Challenge Of Marked Cardiac-Specific Overexpression Of Adenylyl Cyclase Type 8

Tarasov

Chakir

Riordon

et al. 2022

Preprint

View full text Add to dashboard Cite

Adult mice with a marked increase in Adenylyl cyclase (AC) activity due to cardio-specific over expression of adenylyl cyclase (AC) type VIII (TGAC8) have an incessantly cardiac work load adapt to this chronic, severe cAMP stress for up to a year without signs of heart failure and without excessive mortality compared to wild-type littermates (WT). Here we focused on mechanisms that underly the TGAC8 adaptive paradigm.Although TGAC8 mice had a 30% increase in both HR and cardiac output, a 23% increase in EF (echocardiography), neither total LV mass nor pathologic hypertrophy biomarkers differed by genotype. Compared to WT the LV cavity volume was reduced in TGAC8, but was encased by thicker LV walls, harboring populations of both smaller cardiac myocytes, and small non-cardiac interstitial cells having increased nuclear EdU labeling. Protein synthesis, proteosome activity, autophagy, Nrf-2 and Hsp90α proteins were also increased in TGAC8 vs WT, but super-oxide radicals did not differ. Despite an apparently marked increased energy demand due to a chronically increased cardiac workload in the context of a chronically increased HR and EF, steady-state LV ATP and phosphocreatine in vivo did not differ in TGAC8 vs WT. Further Acc2, known to suppress fatty acid oxidation and to increase aerobic glycolysis in the context of enhanced utilization of the pentose phosphate shunt, and NADH/NADPH cycling were both elevated in TGAC8 vs WT mice.Unbiased omics unveiled additional genotypic differences in the potential mechanisms involved in the chronically increased TGAC8 heart performance and the adaptive paradigm in response to this chronic stress. 2,323 transcripts and 2,184 proteins, spanning a wide array of biological processes and molecular functions in numerous cellular compartments, including over 250 canonical signaling pathways, that integrate stress responses, cytokine and T cell receptor signaling, immune responses, ROS scavenging, protection from apoptosis, and nutrient sensing, were activated in TGAC8 vs WT. Several adaptive mechanisms that limit cAMP/PKA signaling were also activated in TGAC8.Thus, in addition to markedly increased cardiac work, the chronic, intense AC-PKA-Ca2+ signaling within the adult TGAC8 heart concurrently activates a consilience of adaptive mechanisms within the TGAC8 LV that resemble survival mechanisms within cancer cells.

show abstract

The rational use of β‐adrenoceptor blockers in the treatment of heart failure. The changing face of an old therapy

Cited by 22 publications

References 46 publications

Plasma membrane‐associated nucleoside diphosphate kinase (nm23) in the heart is regulated by β‐adrenergic signaling

Plasma membrane‐associated nucleoside diphosphate kinase (nm23) in the heart is regulated by β‐adrenergic signaling

Anatomy, Physiology, and Pathophysiology of Erectile Dysfunction

A Remarkable Adaptive Paradigm Of Heart Performance And Protection Emerges In Response To The Constitutive Challenge Of Marked Cardiac-Specific Overexpression Of Adenylyl Cyclase Type 8

Contact Info

Product

Resources

About