Cross-talk with β2-adrenoceptors enhances ligand affinity properties from endothelial alpha1D-adrenoceptors that mediates carotid relaxation

Objectives Our main objectives were to investigate the affinity properties of endothelial and muscular α1D-adrenoceptors and to characterize the cross-talk between endothelial α1D- adrenoceptors and β2-adrenoceptors in rat carotid. Methods Relaxation and contraction concentration-response curves for phenylephrine (α1-adrenergic agonist) were obtained in carotid rings in absence or presence of increasing concentrations of BMY7378 (α 1D-adrenergic antagonist), combined or not with increasing concentration of ICI-118,551 (β2-adrenergic antagonist). Schild analysis was used to estimate the affinity constant from pA2 values of BMY7378. Key Findings BMY7378 produced an unsurmountable antagonism on phenylephrine-induced relaxation but a surmountable antagonism on phenylephrine-induced contraction. BMY7378 potency was higher in inhibiting the relaxation than the contraction induced by phenylephrine because the rightward shifts induced by BMY7378 were greater in the relaxation. The apparent pA 2 value for BMY7378 in phenylephrine-induced relaxation was greater than in contraction. When combined with ICI-118,551, BMY7378 yielded a surmountable antagonism on phenylephrine-induced relaxation and presented a pA2 value similar to that obtained in phenylephrine-induced contraction. Conclusions Endothelial α1D-adrenoceptors, which mediates rat carotid relaxation, present high ligand affinity because of the cross-talk with β2-adrenoceptors, which explains the higher potency of phenylephrine in inducing relaxation than contraction and the atypical unsurmountable antagonism produced by BMY7378 on phenylephrine-induced relaxation. © 2013 Royal Pharmaceutical Society.

Stress susceptibility in pigs supplemented with ractopamine

Ractopamine is a β-adrenergic agonist used as an energy repartitioning agent in the diets of finishing pigs. Most ractopamine studies are limited to evaluations of growth performance and meat quality, and there is little information on the effects of this additive on the behavior and welfare of pigs. Therefore, the objective of this study was to evaluate various indicators of stress caused by feeding diets containing ractopamine. One hundred seventy barrows and 170 gilts weighing 107.3 kg were allocated to 30 pens with 10 to 12 barrows or gilts per pen. Pigs were offered 1 of the 3 dietary treatments (0, 5, or 10 mg ractopamine/kg) for 28 d with 5 barrow pens and 5 gilt pens per treatment. Pigs were evaluated for behavior 3 d per week 1 wk before the initiation of the experiment and throughout the experiment. Each pig was classified into 1 of the 13 activities (drinking water, lying alone, lying in clusters, standing, nosing pig, sitting, feeding, biting pig, walking, exploring, running away, playing, and mounting pen mates) and also grouped into 1 of the 3 categories (calm, moving, and feeding themselves) based on those activities. At the end of the experiment, 3 pigs from each pen were slaughtered, and blood samples were collected during exsanguination to determine physiological indicators of stress (cortisol, lactate, and creatine-kinase enzymes). The incidence of skin and carcass lesions was determined at shoulder, loin, and ham. Ractopamine had no effect (P > 0.05) on pig behavior, total number of skin and carcass lesions, or blood concentrations of cortisol or lactate. However, there was an increase (P < 0.05) of creatine kinase concentrations in pigs receiving ractopaminesupplemented feed. This finding is consistent with the concept that ractopamine may cause muscular disorders, and this warrants further investigation. © 2013 American Society of Animal Science. All rights reserved.

Commissural nucleus of the solitary tract regulates the antihypertensive effects elicited by moxonidine

The rostral ventrolateral medulla (RVLM) contains the presympathetic neurons involved in cardiovascular regulation that has been implicated as one of the most important central sites for the antihypertensive action of moxonidine (an α2-adrenergic and imidazoline agonist). Here, we sought to evaluate the cardiovascular effects produced by moxonidine injected into another important brainstem site, the commissural nucleus of the solitary tract (commNTS). Mean arterial pressure (MAP), heart rate (HR), splanchnic sympathetic nerve activity (sSNA) and activity of putative sympathoexcitatory vasomotor neurons of the RVLM were recorded in conscious or urethane-anesthetized, and artificial ventilated male Wistar rats. In conscious or anesthetized rats, moxonidine (2.5 and 5. nmol/50. nl) injected into the commNTS reduced MAP, HR and sSNA. The injection of moxonidine into the commNTS also elicited a reduction of 28% in the activity of sympathoexcitatory vasomotor neurons of the RVLM. To further assess the notion that moxonidine could act in another brainstem area to elicit the antihypertensive effects, a group with electrolytic lesions of the commNTS or sham and with stainless steel guide-cannulas implanted into the 4th V were used. In the sham group, moxonidine (20. nmol/1. μl) injected into 4th V decreased MAP and HR. The hypotension but not the bradycardia produced by moxonidine into the 4th V was reduced in acute (1. day) commNTS-lesioned rats. These data suggest that moxonidine can certainly act in other brainstem regions, such as commNTS to produce its beneficial therapeutic effects, such as hypotension and reduction in sympathetic nerve activity. © 2013 IBRO.

Participação das vias alfa 2 - adrenérgica, dopaminérgica e gabaérgica no controle da secreção de GH no período pré-púbere de novilhas da raça nelore

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Desempenho, qualidade de carne e estresse de suínos suplementados com ractopamina

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparação dos efeitos do sufentanil e da clonidina administrados por via endovenosa para sedação em pacientes submetidos a cateterismo cardíaco

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Sevoflurano e dexmedetomidina em isquemia e reperfusão renais no rato

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Role of α2-adrenoceptors in the lateral parabrachial nucleus in the control of body fluid homeostasis

Central α2-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α2-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α2-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α2-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α2-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α2-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.

Effects of catecholamines on volemic replacement with saline solution and the impact on heart rate variability in rabbits subjected to hemorrhage. A study by spectral analysis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Susceptibilidade ao estresse e qualidade de carne de suínos suplementados com diferentes níveis de Ractopamina

The ractopamine is a β-adrenergic agonist used as a divider of energy in diets for finishing pigs. However, research shows that this additive may effect on welfare and meat quality. In this context, the aim was to evaluate the influence in three levels of inclusion of ractopamine (0, 5 and 10ppm) in commercial pigs diet (castrated, males and females, n = 340) for 28 days pre-slaughter on the welfare and meat quality. The wellbeing was assessed by the behavior of animals, number of skin damages, carcass damages and physiological stress (lactate, cortisol and creatinine phosphokinase). The evaluation of meat quality was performed by analyzing pH, color, drip and cooking loss, shear force and marbling of the longissimus dorsi muscle of 90 selected pigs. There was no influence of treatments on the behavior, the total number of skin damages and carcass damages or concentration of cortisol and lactate. However, levels of the enzyme creatine phosphokinase (CPK) increased in pigs supplemented with ractopamine. This shows that, somehow, this additive led to physiological changes in animals that consumed it. PH and drip loss did not change by the addition of ractopamine in the diet. In contrast, the Longissimus dorsi of pigs that received ractopamine presented less intense red color and no difference was found in L* and b*. The inclusion of ractopamine in the diet reduced the degree of marbling, cooking loss and tenderness of the muscle. Supplementation did not lead to behavioral change, increased incidence of injury, plasma cortisol and lactate and minimal impact on meat quality. However, there was evidence that the animals fed the additive suffered physiological changes

Induction of multiple ovulations in mares using low doses of GnRH agonist Deslorelin Acetate at 48 hours after luteolysis

This study was aimed to test low doses of a GnRH agonist, deslorelin acetate (DA), for induction of multiple ovulations in mares and to determine its impact upon their reproductive efficiency. Seven mares aging from 8-20 years were used in three consecutive reproductive cycles. Mares were initially monitored by ultrasound irrespectively of cycle stage, inseminated and submitted to embryo collection (EC) (T1). Immediately after, mares received 7.5 mg dinoprost tromothamine (DT) and were monitored by ultrasound twice a day until larger follicle reached 23-25mm and the second >18mm (T2). At this time point, mares received 100 mu g DA and ovulation was induced with 1000 mu g DA and 1000IU hCG when largest follicle reached 33-35mm in diameter, followed by EC. Mares were further allocated to T3 when received 7.5 mg DT after EC on 12 and 100 mu g DA 48 h later. DA treatment was performed until dominant follicle reached 34 +/- 1 mm or 6 days of application. All EC were performed 8 days after ovulation. Mares with multiple ovulations in T1, T2 and T3 were 14.28% (1/7), 100.00% (7/7) and 0.00% (0/7), respectively, and averaged 0.43 +/- 0.53 in T1, 0.86 +/- 0.38 in T2 and 0.00 in T3 embryos per donor, respectively. Embryo recovery rate was 43.00% in T1, 85.71% in T2 and 0.00% T3. In conclusion, use of DA in mares with follicles larger than 25mm enhanced dominant and co-dominant follicle growth, that ultimately increased the incidence of multiple ovulations and embryo recovery rate.

Imunocastração e ractopamina na qualidade de lombos suínos processados com sal e tripolifosfato

The objective of this work was to evaluate the effect of immunocastration and supplementation with ractopamine in the quality of pork loin enhanced with salt and sodium tripolyphosphate. Treatments consisted of the sexual condition of the swine (females, physically castrated and immunocastrated males) and supplementation or not with ractopamine in finishing diet. The loins subjected to the enhancement with sodium tripolyphosphate and salt were evaluated as to physical-chemical, microbiological, and sensory parameters. There was no interaction between sexual condition and ractopamine on fresh pork loin characteristics. The addition of ractopamine in the diet increased the shear force in fresh loins. There was also no effect of sexual condition nor of ractopamine in purge loss and loin protein content. Loins of immunocastrated animals had less weight loss by cooking, whereas loins of animals non-supplemented with ractopamine showed higher moisture than those supplemented. Enhancement decreases the shear force of the cuts, which was lower in the immunocastrated animals without ractopamine supplementation. Immunocastration provided pork loins with high a* and L* values. Differences in the appearance and texture of pork loins, regardless of sexual condition and ractopamine, are not perceived by consumers, showing that enhancement standardizes the cuts.

Polymorphisms in Oxytocin and alpha(1a) Adrenergic Receptor Genes and Their Effects on Production Traits in Dairy Buffaloes

The use of molecular markers may auxiliary the buffalo breeding. The oxytocin (OXT) and the adrenergic receptor alpha(1A) (ADRA1A) may be involved in milk ejection in ruminants. The aim of this study was to verify the existence of polymorphisms in the OXT and ADRA1A genes and their associations with milk production traits. A total of 220 buffaloes were genotyped using PCR-RFLP for both genes. The SNP identified in the ADRA1A gene was associated with protein percentage in dairy buffaloes. This is the first report of such association in the literature, which has not been studied in other species.

Effect of an acute β-adrenergic blockade on the blood glucose response during lactate minimum test

The aim of this study was to determine the relationship between blood lactate and glucose during an incremental test after exercise induced lactic acidosis, under normal and acute β-adrenergic blockade. Eight fit males (cyclists or triathletes) performed a protocol to determine the intensity corresponding to the individual equilibrium point between lactate entry and removal from the blood (incremental test after exercise induced lactic acidosis), determined from the blood lactate (Lacmin) and glucose (Glucmin) response. This protocol was performed twice in a double-blind randomized order by ingesting either propranolol (80 mg) or a placebo (dextrose), 120 min prior to the test. The blood lactate and glucose concentration obtained 7 minutes after anaerobic exercise (Wingate test) was significantly lower (p<0.01) with the acute β-adrenergic blockade (9.1±1.5 mM; 3.9±0.1 mM), respectively than in the placebo condition (12.4±1.8 mM; 5.0±0.1 mM). There was no difference (p>0.05) between the exercise intensity determined by Lacmin (212.1±17.4 W) and Glucmin (218.2±22.1 W) during exercise performed without acute β-adrenergic blockade. The exercise intensity at Lacmin was lowered (p<0.05) from 212.1±17.4 to 181.0±15.6 W and heart rate at Lacmin was reduced (p<0.01) from 161.2±8.4 to 129.3±6.2 beats min-1 as a result of the blockade. It was not possible to determine the exercise intensity corresponding to Glucmin with β-adrenergic blockade, since the blood glucose concentration presented a continuous decrease during the incremental test. We concluded that the similar pattern response of blood lactate and glucose during an incremental test after exercise induced lactic acidosis, is not present during β-adrenergic blockade suggesting that, at least in part, this behavior depends upon adrenergic stimulation.

Role of central α1- and α2-adrenoceptors on the dipsogenic and cardiovascular effect of angiotensin II

We investigated the effects of previous central treatment with prazosin (an α1-adrenoceptor antagonist) or clonidine (an α2-adrenoceptor agonist) on the dipsogenic, pressor and tachycardic responses produced by intracerebroventricular (ICV) injection of angiotensin II (AII) in conscious rats. Holtzman rats with a chronic cannula implanted in the lateral ventricle were tested for dipsogenic and cardiovascular (arterial pressure and heart rate) responses in separate experiments. Previous ICV treatment with clonidine (20, 40, 80 and 120 nmol) abolished the pressor, tachycardic and dipsogenic effects of ICV AII. After all doses of prazosin (40, 80 and 120 nmol), AII induced bradycardic responses, but only the 80 and 120 nmol doses of prazosin reduced the pressor responses to AII. Prazosin produced no alteration in the dipsogenic effect of AII. The results show that the periventricular α1-adrenoceptors are involved only in the cardiovascular responses produced by central AII, whereas clonidine acting through α2-adrenergic and/or imidazole receptors can modulate all actions of AII. © 1990.