Targeting Nitric Oxide With Drug Therapy

Mason, R. Preston; Cockcroft, JR

doi:10.1111/j.1524-6175.2006.06041.x

Cited by 46 publications

(38 citation statements)

References 155 publications

(337 reference statements)

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“…function and cardiovascular physiology. 11,12 Nebivolol has also been shown to increase NO bioactivity, both in healthy volunteers and in patients with hypertension. 13−15 Agents that increase NO bioactivity may provide cardiovascular benefits beyond BP-lowering effects.…”

Section: Discussionmentioning

confidence: 99%

Nebivolol Efficacy and Safety in Patients with Stage I‐II Hypertension

Greathouse¹

2010

Clinical Cardiology

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Background: Nebivolol is a novel, β 1 -adrenergic receptor blocker with vasodilatory properties mediated through activation of the L-arginine/nitric oxide pathway. Hypothesis: This multicenter, double-blind, parallel-group, placebo-controlled study investigated the antihypertensive efficacy and safety of nebivolol in patients with stage I through stage II hypertension (sitting diastolic blood pressure [SiDBP] ≥95 mm Hg and ≤109 mm Hg). Methods: A total of 811 patients were randomized to placebo or nebivolol 5 mg, 10 mg, or 20 mg once daily for 12 weeks. The primary efficacy endpoint was the reduction in mean trough SiDBP from baseline. Results: At study end, the least squares mean reductions in trough SiDBP from baseline with nebivolol 5 mg, 10 mg, and 20 mg were −7.8 mm Hg, −8.5 mm Hg, and −9.1 mm Hg, respectively, compared with −4.6 mm Hg for placebo (P = .002 for nebivolol 5 mg, P<.001 for nebivolol 10 mg and 20 mg, vs placebo). Nebivolol treatment also produced reductions in trough sitting systolic blood pressure; however, only the 20 mg dose was statistically significant compared with placebo (−6.7 mm Hg vs −0.4 mm Hg; P<.001). Response rates (defined as an average trough SiDBP <90 mm Hg or a decrease by ≥10 mm Hg from baseline at the end of the study) ranged from 66.0% to 68.9% with nebivolol 5-20 mg, compared with 49.3% with placebo (P≤.009). Nebivolol 5 mg and 10 mg doses were well tolerated, with an overall adverse event incidence comparable to placebo. Conclusions: Once-daily nebivolol is an effective antihypertensive agent in patients with stage I-II hypertension.

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Section: Discussionmentioning

confidence: 99%

Nebivolol Efficacy and Safety in Patients with Stage I‐II Hypertension

Greathouse¹

2010

Clinical Cardiology

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“…On the other hand, nitroglycerin has many more therapeutic options, as in the treatment of angina, congestive heart failure, unstable angina pectoris, non-ST-segment-elevation myocardial infarction, acute myocardial infarction, and variant angina [72]. Tolerance to nitroglycerin can occur with long-term usage, but the vitamins C or E, which are antioxidants, along with the organic nitrate therapy have been shown to prevent tolerance to the drug [75]. Our lab, in 1995, demonstrated the beneficial effects of nitroprusside on the ischemically damaged rat kidney, concluding that exogenous NO is beneficial and protective to the kidney during I/R [76].…”

Section: Exogenous Nitric Oxide Donorsmentioning

confidence: 99%

Nitric Oxide Mechanism of Protection in Ischemia and Reperfusion Injury

Phillips

Toledo

López-Neblina

et al. 2009

Journal of Investigative Surgery

176

107

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In 1992 nitric oxide (NO) was declared molecule of the year by Science magazine, and ever since research on this molecule continues to increase. Following this award, NO was shown to be a mediator/protector of ischemia and reperfusion injury in many organs, such as the heart, liver, lungs, and kidneys. Controversy has existed concerning the actual protective effects of NO. However, literature from the past 15 years seems to reinforce the consensus that NO is indeed protective. Some of the protective actions of NO in ischemia and reperfusion are due to its potential as an antioxidant and anti-inflammatory agent, along with its beneficial effects on cell signaling and inhibition of nuclear proteins, such as NF-kappa B and AP-1. New therapeutic potentials for this drug are also continuously emerging. Exogenous NO and endogenous NO may both play protective roles during ischemia and reperfusion injury. Sodium nitroprusside and nitroglycerin have been used clinically with much success; though only recently have they been tested and proven effective in attenuating some of the injuries associated with ischemia and reperfusion. NO inhalation has, in the past, mostly been used for its pulmonary effects, but has also recently been shown to be protective in other organs. The potential of NO in the treatment of ischemic disease is only just being realized. Elucidation of the mechanism by which NO exerts its protective effects needs further investigation. Therefore, this paper will focus on the mechanistic actions of NO in ischemia and reperfusion injury, along with the compound's potential therapeutic benefits.

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“…[9][10][11] Agents that restore vascular NO bioavailability may therefore have important therapeutic advantages in the treatment and prevention of cardiovascular disease. 12 β-Blockers are recommended as the first line of therapy for hypertension and are indicated for patients with various comorbid conditions such as diabetes mellitus. 13 Nebivolol is a highly selective β 1 -adrenergic receptor antagonist with direct vasodilatory properties.…”

mentioning

confidence: 99%