Effects of Cardioselective Beta Blocker Nebivolol on Different Biochemical Parameters in Essential Hypertensive Patients.

Background : Nebivolol is a third-generation highly selective b1-blocker with additional endothelial nitric oxide (NO) mediated vasodilating activity. This property may potentiate the blood pressure-lowering effect of Nebivolol. Nebivolol is also claimed to have neutral or favourable effect on carbohydrate metabolism and lipid profile. Therefore this study was conducted to evaluate effects of Nebivolol on different biochemical parameters in essential hypertensive patients. Materials and Methods : 21 newly diagnosed patients of either sex with essential hypertension were included in the study. Patients having co-morbidities e.g. Diabetes mellitus, hyperlipidemia, gout, pregnant females were excluded from the study. Baseline readings of lipid profile, serum electrolytes, fasting blood sugar and uric acid were recorded before starting Nebivolol drug therapy. Same biochemical tests were repeated after six months drug treatment. Results and Observation : After comparing the means there is increase in total cholesterol, LDL, Serum electrolytes, blood sugar levels but this increase is within normal limits and is not statistically significant. While there is decrease in TG level but statistically not significant. No significant change in HDL, uric acid levels. Conclusion : Nebivolol is a unique, highly selective b1-blocker due to its neutral metabolic properties and is potentially safe over conventional b-blockers.

Involvement of β3-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 β3-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 β3-adrenergic receptors within the central nervous system. Moreover, they suggest the involvement of these receptors in the control of anxiety.

Função endotelial vascular em pacientes com fluxo coronário lento e os efeitos do nebivolol / Vascular endothelial function in patients with coronary slow flow and the effects of nebivolol

FUNDAMENTO: A função endotelial braquial tem sido associada ao fluxo lento coronário (FLC). O aumento do fluxo sanguíneo para a artéria braquial faz com que o endotélio libere óxido nítrico (ON), com subsequente vasodilatação. Além de sua atividade com betabloqueador, o nebivolol provoca vasodilatação, aumentando a liberação endotelial de ON. OBJETIVO: Avaliar os efeitos do nebivolol na função endotelial vascular em pacientes com FLC. MÉTODOS: 46 pacientes com FLC e 23 indivíduos com artérias coronárias epicárdicas normais foram examinados com ecocardiografia transtorácica e ultrassonografia da artéria braquial. Os pacientes foram reavaliados dois meses após o tratamento com aspirina ou aspirina e nebivolol. RESULTADOS: Os pacientes com FLC apresentaram maior índice de massa corporal (26,5 ± 3,3 vs. 23,8 ± 2,8, p < 0,001), tempo de relaxamento isovolumétrico (TRIV) de influxo mitral (114,9 ± 18,0 vs. 95,0 ± 22,0 mseg, p < 0,001), menor fração de ejeção do ventrículo esquerdo (FEVE) (63,5 ± 3,1 por cento vs. 65,4 ± 2,2, p = 0,009), colesterol HDL (39,4 ± 8,5 vs. 45,8 ± 7,7 mg/dL, p = 0,003) e dilatação fluxo-mediada da artéria braquial (DFM) (6,1 ± 3,9 por cento vs. 17,6 ± 4,5 por cento, p <0,001). Houve correlações significativas entre a DFM e a presença de FLC (r = 0,800, p < 0,001) e o colesterol HDL (r = 0,349, p = 0,003). Dos pacientes com FLC, apesar de os valores médios de DFM em pré-tratamento terem sido semelhantes (6,1 ± 4,3 por cento vs. 6,0 ± ,6 por cento, p = 0,917), em comparação com a DFM do grupo em pós-tratamento apenas com aspirina, a DFM apresentou valores significativamente maiores do que os pacientes tratados com aspirina e nebivolol (6,0 ± 3,5 por cento vs. 8,0 ± 2,9 por cento, p = 0,047). Constatou-se que o tratamento com nebivolol está associado a um significativo aumento na DFM (6,0 ± 3,6 a 8,0 ± 2,9 por cento, p = 0,030), ao passo que o tratamento apenas com aspirina não apresentou a mesma associação. CONCLUSÃO: A função endotelial pode ser comprometida nas artérias coronárias e braquiais em pacientes com FLC, e o nebivolol pode ser eficaz na melhora da função endotelial em pacientes com FLC.

BACKGROUND: Brachial endothelial function has been associated with coronary slow flow (CSF). Increasing blood flow to brachial artery provokes endothelium to release nitric oxide (NO) with subsequent vasodilatation. Besides its β1-blocker activity, nebivolol causes vasodilatation by increasing endothelial NO release. OBJECTIVE: To assess the effects of nebivolol on vascular endothelial function in patients with CSF. METHODS: Forty-six patients with CSF and 23 individuals with normal epicardial coronary arteries were examined with transthoracic echocardiography and brachial artery ultrasonography. The patients were reevaluated two months after treatment with aspirin or aspirin plus nebivolol. RESULTS: Patients with CSF had higher body mass index (26.5 ± 3.3 vs. 23.8 ± 2.8, p < 0.001), mitral inflow isovolumetric relaxation time (IVRT) (114.9 ± 18.0 vs. 95.0 ± 22.0 msec, p < 0.001) and lower left ventricular ejection fraction (LVEF) (63.5 ± 3.1 percent vs. 65.4 ± 2.2, p = 0.009), HDL-cholesterol (39.4 ± 8.5 vs. 45.8 ± 7.7 mg/dL, p = 0.003) and brachial flow-mediated dilatation (FMD) (6.1 ± 3.9 percent vs. 17.6 ± 4.5 percent, p < 0.001). There were significant correlations between FMD and the presence of CSF (r = 0.800, p < 0.001) and HDL-cholesterol (r = 0.349, p = 0.003). Among Patients with CSF, although pretreatment mean FMD values were similar (6.1 ± 4.3 percent vs. 6.0 ± ,6 percent, p = 0.917) compared to aspirin alone group, posttreatment FMD was significantly higher in patients treated with aspirin plus nebivolol (6.0 ± 3.5 percent vs. 8.0 ± 2.9 percent, p = 0.047). Treatment with nebivolol was associated with a significant increase in FMD (6.0 ± 3.6 to 8.0 ± 2.9 percent, p = 0.030) whereas treatment with aspirin alone was not. CONCLUSION: Endothelial function may be impaired in both coronary and brachial arteries in patients with CSF and nebivolol may be effective in the improvement of endothelial function in patients with CSF.

Linear free-energy relationships in series of alkanolamines as lysosomotropic agents and choline uptake inhibitors

The solvation parameters model was used to develop a series of statistically significant linear free-energy relationship [LFER] associating lipophilicity [expressed as the logarithm of partition coefficients in n-octanol/water system, log P oct] of 25 diverse alkanolamines with their five structural descriptors constituting the general solvation parameters model proposed by Abraham [1989], as V x, the McGowan [1987] characteristic volume R 2, the excess of molar refraction [PI] H, the dipolarity/polarizability, sigma alpha H, the hydrogen-bond acidity, and sigma beta H, the effective hydrogen-bond basicity. A modified set of the fragmental constants for estimation of PI H, sigma alpha H, and sigma beta H, descriptors of individual alkanolamines has been proposed and applied to calculations of LFER by the multivariate regression procedure. Similary, LFER were established for the experimental values of logarithms of reciprocal of the minimal bactericidal concentration [log[1/MBC]] in a series of lysosomotropic alkabikanubes as reported by Sandin et al. [1992]. The calculated LFER model demonstrates that molecular size [V x term] and effective hydrogen-bond acidity [sigma alpha H term] are the most important structural parameters favouring the transport of uncharged forms of alkanolamines through the bacterial cytoplasmic membrane and their accumulation in bacterial cells. The LFER approach was also applied to experimental data relating 14 alkanolamines as the inhibitors of choline uptake into murine L1210 leukemia cells reported by Naujokaitis et al. [1984]. In this case the established LFER shows that the crucial factors which determine the inhibition of choline transport by alkanolamines are specific dispersion interactions [R 2 term], molecular size [V x term] and effective hydrogen-bond basicity [sigma beta H term] that decreases observed inhibition. The results of the studies presented indicate LFER as a suitable method for the pre-selection of the alkanolamines with defined molecular characteristics for the in vivo chemotherapy of lymphocytic leukemia

Metabolic markers following beta-adrenoceptor agonist infusion in footshock-stressed rats

Stress hormones can alter metabolic functions in adipose tissue and liver, as well as the sensitivity of rat white adipocytes and rat atrial responses to ß-adrenergic agonists. In this study, we examined the effects of three daily footshock stress sessions on the plasma corticosterone, glucose, glycerol and triacylglycerol levels of fed, conscious male rats, and on the plasma glucose, glycerol and triacylglycerol levels of the same rats following iv infusions of ß-adrenergic agonists (isoproterenol: 0.4 nmol kg-1 min-1, noradrenaline: 5.0 æg kg-1 day-1, and BRL 37344 ([+ or -]-[4-(2-[(2-[3-chlorophenyl]-2-hydroxyethyl)amino]propyl)phenoxy]acetic acid), a selective ß3-adrenoceptor agonist: 0.4 nmol kg-1 min-1). Plasma corticosterone levels increased significantly after each stress session, while triacylglycerol levels increased after the first session and glucose increased after the second and third sessions. Glycerol levels were unaltered after stress. These results suggest that repeated footshock stress may induce a metabolic shift from triacylglycerol biosynthesis to glucose release by hepatic tissue, with glycerol serving as one of the substrates in both pathways. Stressed rats were more sensitive to infusion of noradrenaline plus prazosin and to infusion of isoproterenol, with elevated plasma glucose, glycerol and triacylglycerol levels. The higher sensitivity of stressed rats to isoproterenol and noradrenaline was probably related to the permissive effect of plasma corticosterone. Only BRL 37344 increased plasma glycerol levels in stressed rats, probably because ß3-adrenoceptors are not involved in hepatic triacylglycerol synthesis, thus allowing glycerol to accumulate in plasma

Systemic effects of ethanolamine oleate: an experimental study

An experimental study for the systemic effects of 5% ethanolamine oleate was conducted on 46 rats, divided into 3 main groups. Rats in group A were subdivided into 3 subgroups of 5 animals each. They were injected once intraperitoneally with 2, 4 and 5 ml of the drug respectively. None of the animals showed any sign of acute toxicity. Histological examination was performed 24 hours after the injection to the liver, spleen, kidneys, heart, lungs, brain, blood and bone marrow and it did not reveal any abnormality. Group B included 28 rats, which were studied for the chronic effect of the drug. They were sub- divided into 4 subgroups, which were injected daily with 0.5 ml of 5% ethanolamine oleate for 2, 4, 6 and 8 weeks respectively. None of the animals died. Histopathological changes were found only in the lungs, affecting 37.5% of the injected animals. There was lymphoid hyperplasia in 20.8%. Interstitial and intraalveolar edema and hemorrhage, with vascular congestion were detected in 25%. There was no correlation between the duration of the injections and the incidence of the lung lesions. Group C included 3 rats, which were injected once in the lower esophagus through a laparotomy. They were given 0.25, 0.5 and 0.75 ml of the drug respectively. Only the rat which was injected with 0.75 ml, developed lung edema, hemorrhage and congestion, when examined 2 weeks after the administration. It can be concluded that 5% ethanolamine oleate is relatively a safe drug. Rats tolerated up to 5 ml single dose without any detectable effect. This dose is equivalent to 180 ml if given to man. However, with frequent repeated doses, there is a potential hazard of injury to the lung capillaries

Estudo das alteraçöes eletrocortigráficas na insuficiência hépatica aguda experimental / Electrocorticographic changes study in experimental acute hepatic failure

Com o objetivo de avaliar o valor da eletrocorticografia no diagnóstico precoce e na caracterizaçäo das alteraçöes que acompanham a insuficiência hepática aguda (IHA) no cobaio, foram empregados 52 animais distribuídos nos seguintes grupos experimentais: a) Grupo Etanolamina-42 animais submetidos à injeçäo de 2,5 ml de Oleato de Monoetanolamina no ducto biliar comum; b) Grupo Controle-10 animais, nos quais foram injetados 2,5 ml de NaCl a 0,9% no ducto biliar comum. Todos os animais foram submetidos a uma pequena cirurgia de implantaçäo de eletrodos, necessária para obtençäo dos registros eletrocorticográficos (ECG). A IHA foi caracterizada por parâmetros clínicos, laboratoriais e anatomopatológicos, com quadro típico de falência hepática aguda. As alteraçöes eletrocorticográficas mostraram preservaçäo do ritmo alfa até um estádio tardio do coma hepático, seguido de uma lentificaçäo progressiva das ondas, aparecimento de complexos trifásicos e por fim, achatamento das ondas e morte cerebral. O método näo foi útil para o diagnóstico precoce do coma hepático, uma vez que as alteraçöes do ECG foram detectadas numa fase em que as manifestaçöes clínicas da IHA eram evidentes. Por outro lado, revelou-se um ótimo recurso para a caracterizaçäo das alteraçöes cerebrais que acompanham a IHA, podendo ser de utilidade no estudo das alteraçöes fisiopatológicas da encefalopatia hepática

Neuropharmacological actions of labetalol.

Labetalol, an alpha- and beta- adrenoceptor antagonist was investigated for its central nervous system effects in rats and mice. A marked reduction in the spontaneous motor activity with no concomittant muscle weakness was produced. The drug caused closure of eyelids in rats. Labetalol caused hypothermia and prolonged the pentobarbitone-induced hyposis. In animals trained for conditioned avoidance response the drug blocked the SCR in all the animals and CAR in a few number of animals. The drug did not protect the animals against electroshock convulsions. From the results it appears that labetalol is a central nervous system depressant.