Nipradilol: A β‐Adrenoceptor Antagonist with Nitric Oxide–Releasing Action

Hayashi, Toshio; Iguchi, Akihisa

doi:10.1111/j.1527-3466.1998.tb00356.x

Cited by 8 publications

(3 citation statements)

References 54 publications

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“…Nipradilol is a relatively new molecule acting as a non selective -blocker and a nitrate-like NO donor [176]. It is commonly used as anti-anginal and hypotensive agent and it has been recognized to possess antiproliferative effects on cultured rat vascular smooth muscle cells [177].…”

Section: Nipradilolmentioning

confidence: 99%

Restoring the Dysfunctional Endothelium

Osto¹,

Coppolino²,

Volpe³

et al. 2007

CPD

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Nowadays the endothelium is considered a key determinant of vascular health. NO is the principal mediator of all endothelial protective effects, due to its antiinflammatory, antiproliferative, immunomodulatory and vasorelaxant properties. On the contrary, a growing body of evidence suggests that endothelial dysfunction is associated with cardiovascular events. Emerging data suggest that acute coronary syndromes (ACS) may involve a complex interplay between endothelial dysfunction, inflammation and thrombosis. Despite the success in reducing the mortality from acute cardiovascular events, the incidence of cardiovascular disease and its complication continues to increase. New insights into mechanisms of endothelial dysfunction, such as a better understanding of the regulation of vascular sources of oxygen radicals, may lead to novel therapeutic strategies with the potential to improve prognosis. The key pharmacological agents that improve clinical outcome in high-risk patients are statins, ACE-inhibitors or angiotensin receptor antagonists. Compelling scientific evidence suggests that these medications are effective in improving endothelial function. The present review focuses on the potential importance of benefits on endothelium of these medicaments in the management of acute coronary syndromes.

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Section: Nipradilolmentioning

confidence: 99%

Restoring the Dysfunctional Endothelium

Osto¹,

Coppolino²,

Volpe³

et al. 2007

CPD

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“…Therefore, ␤ 1 -AR-selective antagonists are more preferred than ␤-AR-non selective antagonists in the treatment of hypertension and angina pectoris. 3,4-Dihydro-8(2-hydroxy-3-isopropylamino)-propoxy-3-nitroxy-2H-1-benzopyran, nipradilol, is designed as a dual-action drug to produce two complementary pharmacological effects; ␤-blockade and nitric oxide releasing action (2) (Fig. 1).…”

mentioning

confidence: 99%

Up-Regulation of Endothelial Nitric Oxide Synthase through β2-Adrenergic Receptor—The Role of a β-Blocker with NO-Releasing Action

Jayachandran

Hayashi

Sumi

et al. 2001

Biochemical and Biophysical Research Communications

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“…1A), which induces vasodilatation (2) and improves glucose metabolism in vivo (3). Because nitric oxide (NO) improves glucose metabolism through vasodilatation of insulin-target tissues (4), nipradilol's antidiabetic effect can be attributed to the NO provision at the level of vasculature.…”

mentioning

confidence: 99%

Effects of Nipradilol, a Nitric Oxide-Releasing β -Adrenoceptor Blocking Agent, on Phosphoenolpyruvate Carboxykinase Gene Transcription in a Rat Hepatoma Cell Line

Yamauchi

Nakajima

Ikeo

et al. 2001

Japanese Journal of Pharmacology

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ABSTRACT-Effects of nipradilol, a b -adrenoceptor blocker with a nitroxy moiety, on phosphoenolpyruvate carboxykinase (PEPCK) gene transcription were examined using a rat hepatoma cell line, H4IIE cells. Dexamethasone was employed as an enhancer of PEPCK gene transcription. Nipradilol, but not timolol (a b-blocker without a nitroxy moiety), attenuated PEPCK gene transcription both in the control and the dexamethasone-treated cells. The effects of nipradilol were eradicated by methylene blue (an inhibitor of cellular guanylate cyclase). Nipradilol is a unique b-blocker that suppresses PEPCK gene transcription in hepatocytes likely through liberation of nitric oxide and resultant activation of guanylate cyclase. Keywords: Dexamethasone, Phosphoenolpyruvate carboxykinase, NipradilolInsulin resistance is an important etiologic abnormality in type 2 diabetes mellitus. Namely, insulin action at the insulin-target tissues such as skeletal muscle and adipose tissue as well as liver is impaired, and much of the hepatic insulin resistance is due to inappropriately increased hepatic gluconeogenesis. Glucocorticoid is a strong diabetogenic hormone that induces insulin resistance both in vitro and in vivo (1). At the level of liver, glucocorticoid increases gluconeogenesis so that it partially mimics the abnormality found in patients with diabetes.Nipradilol, 3,3-dihydro-8-(2-hydroxy-3-isopropylamino) proxy-2H-l-benzopyran, is a potent b-adrenoceptor blocking agent with nitroxy moiety (Fig. 1A), which induces vasodilatation (2) and improves glucose metabolism in vivo (3). Because nitric oxide (NO) improves glucose metabolism through vasodilatation of insulin-target tissues (4), nipradilol's antidiabetic effect can be attributed to the NO provision at the level of vasculature. However, NO inhibition of hepatic phosphoenolpyruvate carboxykinase (PEPCK) activity leading to reduction of gluconeogenesis is also known (5). Therefore, we thought it is possible that nipradilol suppresses hepatic gluconeogenesis through inhibition of PEPCK activity. If so, this would be a novel antidiabetic action of nipradilol that will be of potential clinical benefit.In the present study, we explored such a possibility by evaluating the direct effect of nipradilol on PEPCK gene regulation using a rat hepatoma cell line, H4IIE cells (American Type Tissue Culture Collection, Rockville, MD, USA). Because expression of PEPCK gene is primarily regulated at the level of transcription (6) and glucocorti-*Corresponding author. FAX: +81-263-37-2710 E-mail: keishi@hsp.md.shinshu-u.ac.jp Fig. 1. Structure of nipradilol (A) and timolol (B).

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Nipradilol: A β‐Adrenoceptor Antagonist with Nitric Oxide–Releasing Action

Cited by 8 publications

References 54 publications

Restoring the Dysfunctional Endothelium

Restoring the Dysfunctional Endothelium

Up-Regulation of Endothelial Nitric Oxide Synthase through β2-Adrenergic Receptor—The Role of a β-Blocker with NO-Releasing Action

Effects of Nipradilol, a Nitric Oxide-Releasing β -Adrenoceptor Blocking Agent, on Phosphoenolpyruvate Carboxykinase Gene Transcription in a Rat Hepatoma Cell Line

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