Preventive effect of varenicline on impairment of endothelial function in cerebral vessels induced by acute smoking in rats

Iida, Mami; Iida, Hiroki; Takenaka, Motoyasu; Tanabe, Kumiko; Iwata, Koichi

doi:10.1007/s00540-012-1433-3

Cited by 10 publications

(5 citation statements)

References 12 publications

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“…However, Iida et al 21 showed that varenicline prevented the impairment of endothelial function in cerebral vessels induced by acute smoking in rats. They found that varenicline itself did not change the response to Ach, but prevented the smoking-induced impairment of endothelium-dependent vasodilation.…”

Section: Varenicline-assisted Smoking Cessation and Vascular Endothelmentioning

confidence: 97%

Varenicline-assisted smoking cessation decreases oxidative stress and restores endothelial function

et al. 2014

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Smoking cessation decreases oxidative stress and restores vascular endothelial function. However, a recent meta-analysis suggests that the use of varenicline, a α4β2 nicotinic acetylcholine receptor partial agonist, increases the risk of cardiovascular events. This study was designed to determine the effect of varenicline-assisted smoking cessation on vascular endothelial function. Study subjects were 11 healthy Japanese males (mean age, 54.4 years) without evidence of cardiovascular disease who were eager to quit smoking. Each subject was treated with varenicline titrated up to 1.0 mg twice daily. We evaluated serum derivatives of reactive oxygen metabolites (d-ROMs) as a marker of oxidative stress, and flow-mediated dilation (FMD) of the brachial artery as a marker of vascular endothelial function. Both measurements were performed before and 3 months after completing smoking cessation. All subjects gained weight (average, 1.7 kg) after smoking cessation. However, there were no significant differences in the following parameters before and after smoking cessation: systolic blood pressure, diastolic blood pressure, heart rate, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glucose and hemoglobin A1c. Serum d-ROM levels significantly decreased from 340.7±70.4 to 300.0±43.2 U.CARR (P=0.012), and FMD significantly increased from 3.36±1.26 to 5.25±1.33% (P=0.00067) after smoking cessation. There was an inverse correlation between FMD and serum d-ROM levels (R=-0.377; P=0.043). Our observations suggest that varenicline-assisted smoking cessation restores vascular endothelial function, and this is associated with decreased oxidative stress, despite an increase in body weight. As varenicline-assisted smoking cessation possibly has beneficial effects on vascular endothelial function, it might also reduce cardiovascular risk.

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Section: Varenicline-assisted Smoking Cessation and Vascular Endothelmentioning

confidence: 97%

Varenicline-assisted smoking cessation decreases oxidative stress and restores endothelial function

et al. 2014

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“…Varenicline is a medication used for smoking treatment (FAESSEL et al, 2010) that acts as a partial agonist for nicotinic cholinergic receptors α4β2 and α3β4 and as a total agonist of receptor α7 (CRUNELLE et al, 2009), promoting the same effects as nicotine, but at a lower intensity, without the effects of withdrawal, and prevents exogenous nicotine from binding to the receptors, blocking the reinforcing effects of its continuous use IIDA et al, 2012). Pharmacokinetic is important information for medications that acts in the central nervous system (HENCHOZ et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Proposal of open field test as a model of varenicline pharmacokinetic study in rats

Zaccarelli-Magalhães

Sandini

Fukushima

2018

REV

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Varenicline is a medication used for smoking treatment that acts as a partial agonist for nicotinic cholinergic receptors α4β2 and α3β4 and as a total agonist of receptor α7 in the central nervous system. Pharmacokinetic is important information for medications that acts in the central nervous system. This kind of assay is commonly done by expensive and complex analytical techniques. Therefore, the aim of this study was to evaluate the possibility of using the open field test as a pharmacokinetic model for varenicline in male rats exposed to a single dose of varenicline. Male rats received a single dose orally (gavage) of three different concentrations of varenicline: 0.03 (therapeutic dose for humans), 0.1 and 0.3 mg/kg or water (control group). The open field observations were recorded 30 min, 1, 2, 4, 6, 24, 48, 72 h and 7 days after the administration of varenicline or water. The results showed alterations in locomotion and rearing frequencies, as well as in immobility time observed in open field, which is consistent with this drug’s plasma peak. Consequently, this behavioral test apparently can be considerate as a model for pharmacokinetic evaluation of varenicline.

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“…Thus, the volume of drug of each concentration was 1 ml, respectively. We measured the pial arteriolar diameter around 4 min after the start of infusion, similar to a previous study [5]. Each drug dose was administered after a 20-min wash-out period with aCSF.…”

mentioning

confidence: 99%

Effects of topical and intravenous JM-1232(−) infusion on cerebrovascular reactivity in rats

Iwata

Iida

et al. 2015

J Anesth

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A novel short-acting benzodiazepine receptor agonist, JM-1232(-), has been shown to have a sedative/hypnotic effect and wide safety margin. However, its effect on cerebral vessels is not well known. Therefore, we investigated the cerebrovascular reactivity to topical and intravenous JM-1232(-) and during hypotension or hypercapnia with intravenous administration of JM-1232(-). We used a closed cranial window preparation to measure the changes of cerebral pial arteriolar diameters in isoflurane-anesthetized Sprague-Dawley rats. We first measured the direct effect of topical JM-1232(-). We then determined the effect of intravenous JM-1232(-) and then we measured the response to hypercapnia before and after JM-1232(-) infusion. Finally, we measured the reaction to stepwise induction of hypotension before and after JM-1232(-) infusion. Topical infusion of JM-1232(-) dilated pial arterioles. Intravenous infusion of JM-1232(-) changed pial arterioles by 4.5 ± 2.7 %, 5.0 ± 3.9 %, and -2.8 ± 2.6 % (at 0.1, 0.3, and 1.0 mg/kg/min, respectively). Hypercapnia dilated pial arterioles before and after JM-1232(-) infusion. The diameters of pial arterioles did not change during hypotension before or after intravenous JM-1232(-) infusion. These results indicate that topical JM-1232(-) has a dilative effect on pial arterioles and that intravenous administration of JM-1232(-) may not affect cerebrovascular reactivity to hypotension or hypercapnia.

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Preventive effect of varenicline on impairment of endothelial function in cerebral vessels induced by acute smoking in rats

Cited by 10 publications

References 12 publications

Varenicline-assisted smoking cessation decreases oxidative stress and restores endothelial function

Varenicline-assisted smoking cessation decreases oxidative stress and restores endothelial function

Proposal of open field test as a model of varenicline pharmacokinetic study in rats

Effects of topical and intravenous JM-1232(−) infusion on cerebrovascular reactivity in rats

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