Does nebivolol have renoprotective action in patients with chronic kidney disease conditions? An integrative review.

Systemic arterial hypertension (SAH) is a chronic disease of multifactorial origin and one of the main risk factors for major adverse cardiovascular events (MACE), which are the leading causes of morbidity and mortality worldwide. The pharmacological treatment of SAH involves five main classes of drugs, and Nebivolol (NEB) is one of those drugs, belonging to the class of third generation ß1-adrenoceptors selective blockers. NEB is composed of a racemic mixture of two enantiomers: d-nebivolol, which exerts antagonist effects on ß1-adrenoceptors, and l-nebivolol, a vascular ß3 receptor agonist. There are several studies that report different actions of NEB, not only for the treatment of SAH, but also as an antioxidant agent or even as a protector of renal damage. The aim of this systematic review was to investigate the available evidence regarding the effects of NEB on kidney diseases, evaluating its possible renoprotective action.

Gonadal hormones modulate the responsiveness to local ß-blocker-induced antinociception in the temporomandibular joint of male and female rats.

BACKGROUND: We have previously demonstrated that blockade of ß-adrenoreceptors (ß-AR) located in the temporomandibular joint (TMJ) of rats suppresses formalin-induced TMJ nociceptive behaviour in both male and female rats, but female rats are more responsive. In this study, we investigated whether gonadal hormones modulate the responsiveness to local ß-blocker-induced antinociception in the TMJ of rats. METHODS: Co-administration of each of the selective ß1 (atenolol), ß2 (ICI 118.551) and ß3 (SR59230A)-AR antagonists with equi-nociceptive concentrations of formalin in the TMJ of intact, gonadectomized and hormone-treated gonadectomized male and female rats. RESULTS: Atenolol, ICI 118.551 and SR59230A significantly reduced formalin-induced TMJ nociception in a dose response fashion in all groups tested. However, a lower dose of each ß-AR antagonist was sufficient to significantly reduce nociceptive responses in gonadectomized but not in intact and testosterone-treated gonadectomized male rats. In the female groups, a lower dose of ß1 -AR antagonist was sufficient to significantly reduce nociceptive responses in gonadectomized but not in intact or gonadectomized rats treated with progesterone or a high dose of oestradiol; a lower dose of ß2 -AR antagonist was sufficient to significantly reduce nociceptive responses in gonadectomized but not in intact and gonadectomized rats treated with low or high dose of oestradiol. CONCLUSION: Gonadal hormones may reduce the responsiveness to local ß-blocker-induced antinociception in the TMJ of male and female rats. However, their effect depends upon their plasma level, the subtype of ß-AR and the dose of ß-blockers used.

The action of p-synephrine on hepatic carbohydrate metabolism and respiration occurs via both Ca(2+)-mobilization and cAMP production.

Citrus aurantium extracts, which contain large amounts of p-synephrine, are widely used for weight loss purposes and as appetite suppressants. In the liver, C. aurantium (bitter orange) extracts affect hemodynamics, carbohydrate metabolism, and oxygen uptake. The purpose of the present work was to quantify the action of p-synephrine and also to obtain indications about its mechanism of action, a task that would be difficult to accomplish with C. aurantium extracts due to their rather complex composition. The experimental system was the isolated perfused rat liver. p-Synephrine significantly stimulated glycogenolysis, glycolysis, gluconeogenesis, and oxygen uptake. The compound also increased the portal perfusion pressure and the redox state of the cytosolic NAD(+)/NADH couple. A Ca(2+)-dependency for both the hemodynamic and the metabolic effects of p-synephrine was found. p-Synephrine stimulated both cAMP overflow and the initial Ca(2+) release from the cellular stores previously labeled with (45)Ca(2+). The metabolic and hemodynamic actions of p-synephrine were strongly inhibited by α-adrenergic antagonists and moderately affected by ß-adrenergic antagonists. The results allow to conclude that p-synephrine presents important metabolic and hemodynamic effects in the liver. These effects can be considered as both catabolic (glycogenolysis) and anabolic (gluconeogenesis), they are mediated by both α- and ß-adrenergic signaling, require the simultaneous participation of both Ca(2+) and cAMP, and could be contributing to the overall stimulation of metabolism that usually occurs during weight loss periods.

Blockade of ß1-, ß2- and ß3-adrenoceptors in the temporomandibular joint induces antinociception especially in female rats.

BACKGROUND: Temporomandibular joint (TMJ) receives rich sympathetic innervations that may contribute to TMJ pain through the local release of sympathomimetic amines. The aim of this study was to determine whether blockade of ß-adrenoceptors in the TMJ of male and female rats reduces formalin-induced TMJ nociceptive behaviour. METHODS: We co-administrated each one of the selective ß(1) -, ß(2) - and ß(3) -adrenoceptors antagonists, atenolol, ICI 118.551 and SR59230A, respectively, with formalin in the TMJ of male and proestrus and dioestrus female rats. Because intra-temporomandibular joint formalin induces significantly different concentration-dependent responses among the three groups, with dioestrus females showing greater responses than males or proestrus females, equi-nociceptive formalin concentrations were used to test the effects of the ß-adrenoceptor antagonists. RESULTS: We found that atenolol, ICI 118.551 and SR59230A significantly reduced formalin-induced TMJ nociception in a dose response fashion in both males and females. However, a lower dose of each ß-adrenoceptor antagonist was sufficient to significantly reduce nociceptive responses in females than in males. Administration of the highest doses of each ß-adrenoceptor antagonist in the TMJ contralateral to that receiving formalin did not affect formalin-induced nociception in males and females, confirming the local action of the ß-adrenoceptor antagonists. CONCLUSIONS: We conclude that blockade of ß-adrenoceptors in the temporomandibular joint suppresses formalin-induced TMJ nociceptive behaviour in both males and females but females are more responsive. These findings suggest that the use of ß-blockers in the treatment of TMJ pain might be of benefit, especially in females.

Involvement of ß3-adrenergic receptors in the control of food intake in rats.

This study examined the food intake changes evoked by intracerebroventricular (icv) injection of a selective agonist (BRL37344, 2 and 20 nmol) or antagonist (SR59230A, 10 and 50 nmol) of ß3-adrenergic receptors in 24-h fasted rats (adult male Wistar rats, 200-350 g, N = 6/treatment). The animals were also pretreated with saline icv (SAL) or SR59230A (50 nmol) followed by BRL37344 (20 nmol) or SAL in order to determine the selectivity of the effects evoked by BRL37344 on food intake or the selectivity of the effects evoked by SR59230A on risk assessment (RA) behavior. The highest dose of BRL37344 (N = 7) decreased food intake 1 h after the treatment (6.4 ± 0.5 g in SAL-treated vs 4.2 ± 0.8 g in drug-treated rats). While both doses of SR59230A failed to affect food intake (5.1 ± 1.1 g for 10 nmol and 6.0 ± 1.8 g for 50 nmol), this treatment reduced the RA frequency (number/30 min) (4 ± 2 for SAL-treated vs 1 ± 1 for 10 nmol and 0.5 ± 1 for 50 nmol SR59230A-treated rats), an ethological parameter related to anxiety. While pretreatment with SR59230A (7.0 ± 0.5 g) abolished the hypophagia induced by BRL37344 (3.6 ± 0.9 g), BRL37344 suppressed the reduction in RA frequency caused by SR59230A. These results show that the hypophagia caused by BRL37344 is selectively mediated by ß3-adrenergic receptors within the central nervous system. Moreover, they suggest the involvement of these receptors in the control of anxiety.