Objective: Secondary failure due to late restenosis continues to occur in 30–50% of individuals after PTCA. β-Blockers play an important role in the treatment of CAD. The aim of this study was to investigate the effects of the new β-blocker nebivolol on cell proliferation of human coronary smooth muscle cells (haCSMCs) and endothelial cells (haECs) in comparison to traditional β-blockers. Methods: The effect of nebivolol and other β-blockers on proliferation of HaECs and HaCSMCs was analyzed by bromodeoxyuridine incorporation. Apoptosis was measured by determination of hypodiploid DNA in both cell types. Additionally, in HaECs NO formation, endothelin-1 transcription and secretion were determined. Results: Incubation for 1, 2, 4, 7 or 14 days resulted in a concentration- and time-dependent reduction of proliferation up to 80% in HaECs and HaCSMCs. β-Blockers such as propranolol, metoprolol or bisoprolol did not exert this effect. Nebivolol inhibited accelerated haCSMC proliferation even in the presence of growth factors such as TGFβ1 and PDGF-BB. Nebivolol concentration-dependently induced a moderate apoptosis (10−5 mol/l: 23%) and a decrease of haCSMCs in the S-phase by 66%. HaECs showed comparable results. During nebivolol incubation NO formation of HaCEs increased, while endothelin-1 transcription and secretion were suppressed. Conclusion: Whereas classical β-blockers do not affect cell growth, only nebivolol inhibits haCSMC or haEC proliferation and induces a moderate rate of apoptosis. Furthermore, in HaCEs NO formation increases and endothelin-1 secretion decreases suggesting that nebivolol may represent a β-blocker with great promises in CAD therapy.

/pdf/effects-of-nebivolol-on-proliferation-and-apoptosis-of-human-2npg7o5e90.pdf

Effects of nebivolol on proliferation and apoptosis of human coronary artery smooth muscle and endothelial cells.

Functional β-adrenoceptors (β-AR) have been identified and characterized in blood vessels under in vivo conditions as well as in vascular smooth muscle cells (SMC) grown in culture. Agonist occupancy of β-AR activates adenylyl cyclase (AC) via the stimulatory guanine nucleotide-binding protein (Gs) and leads to elevations in intracellular adenosine 3',5'-cyclic monophosphate levels (cAMP). Increased cAMP activates the cAMP-dependent protein kinase (PKA), with subsequent phosphorylation of various target proteins. This β-AR pathway interacts with several other intracellular signalling pathways via cross-talk, so that activation by β-AR agonists may also modulate other second messengers and protein kinases. SMC β-AR play an important role in SMC function. In intact blood vessels they mediate SMC relaxation by various intracellular mechanisms, ultimately causing a decrease in intracellular Ca2+ levels. In cultured SMC, activation of the β-AR pathway results in inhibition of cellular proliferation, the develo...

Vascular β-adrenoceptor function in hypertension and in ageing

Estrogen receptor-beta knockout mice become hypertensive as they age, and males have a higher blood pressure than females. We hypothesized that the absence of estrogen receptor-beta may contribute to development of cardiovascular dysfunction by modification of adrenergic responsiveness in the peripheral vasculature. Small femoral arteries (internal diameter <200 microm) were isolated from estrogen receptor-beta knockout and wild-type mice and mounted on a wire myograph. Concentration-response curves to phenylephrine and norepinephrine were compared and the contribution of adrenoceptor subtypes established using specific agonists and antagonists. The involvement of endothelial factors in the modulation of resting tone was also investigated and immunohistochemical analysis used to confirm the presence or absence of estrogen receptor expression. Compared with wild type, arteries from estrogen receptor-beta knockout male, but not female, mice demonstrated gender-specific enhancement of the response to phenylephrine (alpha1-adrenoceptor agonist), which was accompanied by elevated basal tension attributable to endothelial factors. Contractile responses to the mixed adrenoceptor agonist norepinephrine did not differ significantly between estrogen receptor-beta knockout and wild type; however, beta-adrenoceptor inhibition unmasked an enhanced underlying alpha1-adrenoceptor responsiveness in estrogen receptor-beta knockout males. beta-adrenoceptor-mediated dilatation was also enhanced in estrogen receptor-beta knockout versus wild-type males. We suggest that estrogen receptor-beta modifies the adrenergic control of small artery tone in males but not in females.

Gender-Specific Alteration of Adrenergic Responses in Small Femoral Arteries From Estrogen Receptor-β Knockout Mice

Stimulation of serum- and glucocorticoid-regulated kinase-1 gene expression by endothelin-1

Modulation of ANP-C receptor signaling by endothelin-1 in A-10 smooth muscle cells.

Elevated endothelin-1 (ET-1) levels are found in atherosclerosis, myocardial ischemia, and heart failure, and are correlated with increased mortality rates. Contrary to expectations, elevations of endogenous ET-I levels in transgenic mice are not associated with increases in arterial blood pressure or with vasospasm, although these effects can be observed after i.v. ET-I administration. The aim of this study was to determine the regulatory effects of ET-1 on the expression of vasodilator β-adrenergic receptors and their ability to activate adenylyl cyclase. Smooth-muscle cells were incubated with ET-1 (10 -7 mol/L) for 3 days. The density of ET-I or β-adrenergic receptor binding sites was determined using a radioligand binding procedure. Adenylyl cyclase activity was measured to assess any functional changes in the β-adrenergic receptor density. ET-I incubation reduced ET-1 binding sites by 70%. In contrast, the β-adrenergic receptor density increased from 354 ± 35 to 538 ± 50 fmol/mg protein (p < 0.01; n = 7) after 3 days. ET-I increased β-adrenergic receptors dose-dependently. Incubation with ET-I for different periods of time showed an initial decrease of 30% after 6 h of ET-1 incubation. However, after 24 h ET-I induced an increase of β-adrenergic receptors. reaching a maximal amount after 48 h. An increased stimulation of β-adrenergic receptor-activated adenylyl cyclase was observed after 3-day ET-I incubation compared to controls. These data demonstrate that chronic ET receptor activation by ET-I results in a functionally significant increase in β-adrenergic receptor density and adenylyl cyclase activity.

Dynamic Regulation of β-Adrenergic Receptors by Endothelin-1 in Smooth-Muscle Cells

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

S. C. Wolf

Author Tools

Chat about Author

Papers

Dynamic Regulation of β-Adrenergic Receptors by Endothelin-1 in Smooth-Muscle Cells