Effect of α1-adrenergic receptors in cardiac pathophysiology

Shannon, Richard P.; Chaudhry, Mohammad Rauf A

doi:10.1016/j.ahj.2006.05.017

Cited by 75 publications

(54 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…20 -22 On top of ␤-blocking effects, carvedilol has been shown to have ␣-blocking properties, which could theoretically be beneficial by reducing the afterload that is increased in chronic AR. 23 High doses carvedilol also have theoretical antioxidant properties that may prove to be protective on a stressed LV myocardium. Our data confirm the ␤-blocking effects (lower heart rate and restoration of ␤-adrenoreceptor expression).…”

Section: Discussionmentioning

confidence: 99%

Usefulness of Carvedilol in the Treatment of Chronic Aortic Valve Regurgitation

Zendaoui

Lachance

Roussel

et al. 2011

Circ: Heart Failure

View full text Add to dashboard Cite

Background-Aortic regurgitation (AR) is a chronic disease for which there is currently no approved medical treatment.We previously reported in an animal model that ␤-blockade with metoprolol exerted beneficial effects on left ventricular remodeling and survival. Despite the recent publication of promising human data, ␤-blockade in chronic AR remains controversial. More data are needed to support this potentially new treatment strategy. We hypothesized that carvedilol might be another safe treatment option in chronic AR, considering its combined ␤-blocking and ␣-blocking effects and proven efficacy in patients with established heart failure. Methods and Results-The effects of a 6-month treatment with carvedilol 30 mg/kg/d orally were evaluated in adult Wistar rats with severe AR. Sham-operated and untreated AR animals were used as controls. Carvedilol treatment resulted in less left ventricular hypertrophy and dilatation. Ejection fraction was improved and filling pressures were reduced by carvedilol. ␤1-Receptor expression was also improved as well as myocardial capillary density. Those beneficial effects were noted despite the presence of drug-induced bradycardia. Conclusions-Carvedilol exerted protective effects against volume-overload cardiomyopathy in this model of aortic valve regurgitation with preserved ejection fraction. These results suggest a protective class effect of ␤-blockers. Combined with the recent publication of promising human data, our findings support the need to carefully design a prospective study in humans to evaluate the effects of ␤-blockers in chronic aortic valve regurgitation. (Circ Heart Fail. 2011;4: 207-213.)

show abstract

Section: Discussionmentioning

confidence: 99%

Usefulness of Carvedilol in the Treatment of Chronic Aortic Valve Regurgitation

Zendaoui

Lachance

Roussel

et al. 2011

Circ: Heart Failure

View full text Add to dashboard Cite

show abstract

“…Unlike some earlier-generation ␤-AR antagonists, carvedilol maintains cardiac output and reduces hypertension by decreasing vascular resistance. Carvedilol has been shown to inhibit agonist binding at ␤ 1 -and ␤ 2 -ARs and also to block norepinephrine binding to ␣ 1 -ARs to reduce vasoconstriction (25,30,37). As a result, the hemodynamic effects of carvedilol are similar to those of renin-angiotensin system blockers and significantly greater than those of conven-tional ␤-AR antagonists such as atenolol (15,17).…”

mentioning

confidence: 63%

Carvedilol binding to β₂-adrenergic receptors inhibits CFTR-dependent anion secretion in airway epithelial cells

Peitzman

Zaidman

Maniak

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Carvedilol functions as a nonselective ␤-adrenergic receptor (AR)/␣1-AR antagonist that is used for treatment of hypertension and heart failure. Carvedilol has been shown to function as an inverse agonist, inhibiting G protein activation while stimulating ␤-arrestin-dependent signaling and inducing receptor desensitization. In the present study, short-circuit current (Isc) measurements using human airway epithelial cells revealed that, unlike ␤-AR agonists, which increase Isc, carvedilol decreases basal and 8-(4-chlorophenylthio)adenosine 3=,5=-cyclic monophosphatestimulated current. The decrease in Isc resulted from inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR). The carvedilol effect was abolished by pretreatment with the ␤2-AR antagonist ICI-118551, but not the ␤1-AR antagonist atenolol or the ␣ 1-AR antagonist prazosin, indicating that its inhibitory effect on Isc was mediated through interactions with apical ␤2-ARs. However, the carvedilol effect was blocked by pretreatment with the microtubuledisrupting compound nocodazole. Furthermore, immunocytochemistry experiments and measurements of apical CFTR expression by Western blot analysis of biotinylated membranes revealed a decrease in the level of CFTR protein in monolayers treated with carvedilol but no significant change in monolayers treated with epinephrine. These results demonstrate that carvedilol binding to apical ␤ 2-ARs inhibited CFTR current and transepithelial anion secretion by a mechanism involving a decrease in channel expression in the apical membrane. inverse agonists; bias ligands; ␤-arrestin signaling; carvedilol

show abstract

“…Animal studies have shown that drugs like amphetamine, methamphetamine, and aminorex, raise 5-HT levels sufficiently to initiate mitogenesis in pulmonary artery smooth muscle cells, thereby activating the signaling cascade that ultimately leads to PAH (30) and ultimately the same histological changes seen in man (31). Mounting evidence indicates that elevated 5-HT concentrations also account for the smooth muscle hypertrophy that is always evident in the hearts of chronic stimulant abusers (32).…”

Section: Resultsmentioning

confidence: 99%

Levamisole, Aminorex, and Pulmonary Arterial Hypertension: A Review

Karch¹,

Vaiano²,

Bertol³

2015

Razavi Int J Med

View full text Add to dashboard Cite

Context: An epidemic of aminorex-associated pulmonary arterial hypertension (PAH), resulting in multiple fatalities, occurred in the 1970s ending only after the drug was removed from the market. In 2009, when it was found that horses de-wormed with the anthelmintic levamisole, metabolized that drug to aminorex, the same drug that caused the 1970s outbreak of PAH. The discovery would not have been cause for concern except to horseracing enthusiasts, who feared horse doping. However, at about the same time the relationship between levamisole and aminorex was discovered, cocaine cartels began adulterating cocaine with levamisole. The rationale for adulterating cocaine with levamisole remains to be established. The purpose of this short review article is to discuss possible reasons for levamisole contamination, new discoveries about the human pharmacokinetics of aminorex, and the possible relationship between aminorex and pulmonary arterial hypertension in man. Evidence acquisition: Medline contents, as well as estimates published by the U.S. drug enforcement agency (DEA), US state department, and the European monitoring center for drugs and drug abuse (EMCDDA) were reviewed and relevant articles retrieved. There is uniform agreement among the various monitoring agencies analyzed.Results: Approximately 70 percent of the U.S. cocaine supply and 40 percent of the European cocaine supply is contaminated with levamisole. Aminorex has the same binding affinities for serotonin and other neurotransmitters as amphetamine. As serotonin is considered to be an important factor in the development of PAH, the possibility of another epidemic of aminorex-induced PAH, this time among cocaine abusers, seems real, and threatening. Conclusions:The results of the first human pharmacokinetic studies of aminorex were first characterized in 2013. The results suggest that while humans could produce aminorex from levamisole, they probably do not convert very much. Even though cases of PAH have been reported in cocaine users, the latest pharmacokinetic studies suggest that very little aminorex is actually produced from the ingested levamisole, probably not enough to cause PAH. However, since both cocaine and aminorex can cause PAH the situation remains unclear. the lack of a clear answer is partially the development of an insidious pulmonary hypertension, producing subtle and non-specific symptoms in its early stages.

show abstract

Effect of α1-adrenergic receptors in cardiac pathophysiology

Cited by 75 publications

References 52 publications

Usefulness of Carvedilol in the Treatment of Chronic Aortic Valve Regurgitation

Usefulness of Carvedilol in the Treatment of Chronic Aortic Valve Regurgitation

Carvedilol binding to β₂-adrenergic receptors inhibits CFTR-dependent anion secretion in airway epithelial cells

Levamisole, Aminorex, and Pulmonary Arterial Hypertension: A Review

Contact Info

Product

Resources

About

Effect of α1-adrenergic receptors in cardiac pathophysiology

Cited by 75 publications

References 52 publications

Usefulness of Carvedilol in the Treatment of Chronic Aortic Valve Regurgitation

Usefulness of Carvedilol in the Treatment of Chronic Aortic Valve Regurgitation

Carvedilol binding to β2-adrenergic receptors inhibits CFTR-dependent anion secretion in airway epithelial cells

Levamisole, Aminorex, and Pulmonary Arterial Hypertension: A Review

Contact Info

Product

Resources

About

Carvedilol binding to β₂-adrenergic receptors inhibits CFTR-dependent anion secretion in airway epithelial cells