The l-enantiomer of nebivolol potentiates the blood pressure lowering effect of the d-enantiomer

Xhonneux, R.; Wouters, Luc; Reneman, Robert S.; Janßen, Paul

doi:10.1016/0014-2999(90)90087-m

Cited by 31 publications

(23 citation statements)

References 5 publications

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“…At 91 days of age the offspring were transported to the Janssen Research Foundation (Beerse, Belgium). After 1 week of acclimatisation (at 98 days of age) the measurement of blood pressure and heart rate was carried out as described previously [14]. Briefly, the animals were anaesthetised with ether and a femoral artery and vein dissected free of surrounding tissue and cannulated.…”

Section: Methodsmentioning

confidence: 99%

Streptozotocin diabetes in the pregnant rat induces cardiovascular dysfunction in adult offspring

et al. 1999

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The hypothesized association between disturbance of the in utero environment and disease in later life is based largely on retrospective epidemiological studies which have focused upon the long-term consequences of in utero malnutrition [1]. Some population-based studies also point to prolonged effects of maternal diabetes on the fetus, including an increase in the frequency of gestational diabetes and of insulin resistance in adult offspring [2,3]. Prospective investigation of potential associations between a diabetic intrauterine milieu and disease in later life has been facilitated by animal models of chemically induced diabetes. These provide a means to evaluate responses to the intrauterine environment per se without the influence of hereditary traits [4±9]. Hyperglycaemia during rat gestation causes perturbations of glucose homeostasis in the offspring [4±9]; adult offspring of rats rendered diabetic with streptozotocin exhibit high plasma insulin concentrations during a glucose tolerance test [5], increased renal clearance of insulin [10] and are strongly resistant to the action of insulin as shown by the eugly- Diabetologia (1999) Summary Severe diabetes in pregnant rats produces persistent metabolic consequences in adult offspring. This study investigated whether diabetes in pregnant rats could also lead to cardiovascular abnormalities in the adult offspring. Blood pressure, heart rate and in vitro vascular reactivity of small arteries were evaluated in female adult offspring of control rats and of rats rendered diabetic with streptozotocin. Rise in blood pressures were similar in both groups of offspring but heart rate was lower in the diabetic offspring (p < 0.05). The rise in blood pressure associated with infusion of a nitric oxide synthase inhibitor was similar in both groups, but the associated decrease in heart rate was more pronounced in diabetic offspring (p < 0.01). Small mesenteric arteries from this group showed enhanced sensitivity to noradrenaline (p < 0.05) and abnormal endothelium-dependent relaxation to acetylcholine (p < 0.01) and bradykinin (p < 0.05). Reduction in acetylcholine induced relaxation, reflected reduced synthesis of nitric oxide or a cyclooxygenase product and was not attributable to an endothelium-derived hyperpolarizing factor. Sensitivity to exogenous nitric oxide was normal. A subgroup of pups born to diabetic dams were suckled by control maternal dams and a subgroup of those born to controls by diabetic dams. Suckling was an important determinant of impaired growth; offspring of diabetic rats suckled by their own mother and those of control rats by diabetic dams showed impaired growth rates whereas growth of offspring of diabetic rats suckled by control dams paralleled those of control rats suckled by their own mother. [Diabetologia (1999)

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Section: Methodsmentioning

confidence: 99%

Streptozotocin diabetes in the pregnant rat induces cardiovascular dysfunction in adult offspring

et al. 1999

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“…The SRRR-enantiomer (d-nebivolol) is a potent and cardioselective _1-adrenergic blocker. The RSSS-enantiomer (l-nebivolol) has a favourable hemodynamic profile, in that normal energy supply during exercise is nor affected [3].…”

Section: Introductionmentioning

confidence: 99%

New Spectrophotometric Determination of Nebivolol in Pharmaceutical Formulation via Charge Transfer Complex

Alhemiary¹

2017

Austin J Anal Pharm Chem

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New simple, sensitive, selective and rapid spectrophotometric methods were developed for the determination of Nebivolol (NBV) in pharmaceutical formulation. The methods are based on charge transfer complexation reaction of NBV as n-electron donor with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), 2,4-dinitrophenol (DNP) and 2,4,6-trinitrophenol (picric acid; PA) as π-acceptors to give highly colored radical anion species. The colored products were quantified spectrophotometrically at 620nm with DDQ (method A), at 525nm with both DNP (method B) and at 500nm with PA (method C). Under the optimized experimental conditions, Beer's law was obeyed over the concentration ranges 4.0-40, 2-25 and 1.0-35 μg/mL with correlation coefficient 0.9983, 9945 and 0.9985 for methods A, B and C respectively. Other method validation parameters, such as precision, accuracy, robustness, ruggedness and selectivity, were satisfactory. The proposed methods were successfully applied to the determination of NBV in commercial tablets. No interference was observed from common tablet adjuvants. Statistical comparison of the results with the reference method showed excellent agreement and indicated no significant difference in accuracy and precision.Keywords: Spectrophotometric; Nebivolol; Charge Transfer Complex selective and sensitive spectrophotometric methods were developed for the determination of NBV. The cited π-acceptors have earlier been employed for the assay of several drug substances [20][21][22] based on similar reaction.

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“…Nebivolol is a new b-blocker with highly selective b 1 -adrenergic receptor blocking and direct vasodilatory properties [9]. The mechanism of vasodilatation is attributed to the generation of NO, an effect that can be inhibited by N G -monomethyl-L-arginine [10].…”

Section: Introductionmentioning

confidence: 99%

Nebivolol has Protective Effect Against Endothelial and Ileal Dysfunction due to I/R

Soydan

Çekiç

Tuncer

2011

Journal of Surgical Research

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The l-enantiomer of nebivolol potentiates the blood pressure lowering effect of the d-enantiomer

Cited by 31 publications

References 5 publications

Streptozotocin diabetes in the pregnant rat induces cardiovascular dysfunction in adult offspring

Streptozotocin diabetes in the pregnant rat induces cardiovascular dysfunction in adult offspring

New Spectrophotometric Determination of Nebivolol in Pharmaceutical Formulation via Charge Transfer Complex

Nebivolol has Protective Effect Against Endothelial and Ileal Dysfunction due to I/R

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