The calibre of the Foramen of Panizza in Crocodylus porosus is variable and under adrenergic control

The foramen of Panizza is located within the outflow tract of the crocodilian heart, between the left and right aortas. It has been suggested that the foremen of Panizza has a variable calibre, which could explain the profound changes in the distribution of flows and pressure profiles recorded in the right and left aortas. We investigated this possibility using a modified in-situ perfused heart preparation in combination with isolated strip preparations from the outflow tract. In the perfused heart preparation, bolus injections of adrenaline increased the resistance in the foramen of Panizza, indicating a decrease in its diameter. Isolated strip preparations from the outflow tract showed a concentration-dependent increase in tension in response to adrenaline, while vasoactive intestinal polypeptide caused a relaxation in adrenaline pre-contracted strip preparations. We propose that an increase in the diameter of the foremen of Panizza may be important during pulmonary to systemic shunts to allow blood to flow from the left to right aorta (reverse foramen flow) in order to supply the carotid and coronary arteries. During non-shunting conditions, a constricted foramen may prevent excess flow from the right to left aorta during diastole.

The phylogeny and ontogeny of autonomic control of the heart and cardiorespiratory interactions in vertebrates

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Structural basis for control of secondary vessels in the long-finned eel, Anguilla reinhardtii

Histological sections of primary segmental arteries and associated interarterial anastomoses and secondary vessels from the long-finned eel Anguilla reinhardtii were examined by light and transmission electron microscopy. Interarterial anastomoses were found to originate from the primary vasculature as depressions through the tunica intima and media, from where they ran perpendicularly to the adventitial layer, before coiling extensively. From here the anastomoses travelled a relatively linear path in the outer margin of the adventitia to anastomose with a secondary vessel running in parallel with the primary counterpart. In contrast to findings from other species, secondary vessels had a structure quite similar to that of primary vessels; they were lined by endothelial cells on a continuous basement membrane, with a single layer of smooth muscle cells surrounding the vessel. Smooth muscle cells were also found in the vicinity of interarterial anastomoses in the adventitia, but these appeared more longitudinally orientated. The presence of smooth muscle cells on all aspects of the secondary circulation suggests that this vascular system is regulated in a similar manner as the primary vascular system. Because interarterial anastomoses are structurally integrated with the primary vessel from which they originate, it is anticipated that flow through secondary vessels to some extent is affected by the vascular tone of the primary vessel. Immunohistochemical studies showed that primary segmental arteries displayed moderate immunoreactivity to antibodies against 5-hydroxytryptamine and substance P, while interarterial anastomoses and secondary vessels showed dense immunoreactivity. No immunoreactivity was observed on primary or secondary arteries against neuropeptide Y or calcitonin gene-related peptide.

A role for histamine in cardiovascular regulation in late stage embryos of the red-footed tortoise, Chelonoidis carbonaria Spix, 1824

A chorioallantoic membrane artery in embryos of the red-footed tortoise, Chelonoidis carbonaria was occlusively cannulated for measurement of blood pressure and injection of drugs. Two age groups of embryos in the final 10 % of incubation were categorized by the ratio of embryonic body to yolk mass. All embryos first received cholinergic and β-adrenergic blockade. This revealed that β-adrenergic control was established in both groups whereas cholinergic control was only established in the older group immediately prior to hatching. The study then progressed as two series. Series one was conducted in a subset of embryos treated with histamine before or after injection of ranitidine, the antagonist of H2 receptors. Injection of histamine caused an initial phasic hypertension which recovered, followed by a longer lasting hypertensive response accompanied by a tachycardia. Injection of the H2 receptor antagonist ranitidine itself caused a hypotensive tachycardia with subsequent recovery of heart rate. Ranitidine also abolished the cardiac effects of histamine injection while leaving the initial hypertensive response intact. In series, two embryos were injected with histamine after injection of diphenhydramine, the antagonist to H1 receptors. This abolished the whole of the pressor response to histamine injection but left the tachycardic response intact. These data indicate that histamine acts as a non-adrenergic, non-cholinergic factor, regulating the cardiovascular system of developing reptilian embryos and that its overall effects are mediated via both H1 and H2 receptor types. © 2013 Springer-Verlag Berlin Heidelberg.

La concentración de calcio iónico se asocia a la presencia de fibrilación auricular post operatoria en pacientes llevados a revascularización miocardica

Objetivo. Determinar en un grupo de pacientes llevados a revascularización miocárdica si existió asociación entre la presencia de niveles de calcio iónico inferiores a 1,1 en las 24 horas del post operatorio y la ocurrencia de fibrilación auricular post operatoria. Metodología. Estudio observacional, analítico de casos y controles, en donde de manera consecutiva se incluyeron 110 sujetos (57 en el grupo de casos con presencia de fibrilación auricular post operatoria y 54 en el grupo de controles sin evidencia de fibrilación auricular) estos sujetos fueron llevados a revascularización miocárdica en la Fundación Cardioinfantil en los años 2010 a 2015. Resultados. Hubo 13 casos de fibrilación auricular post operatoria en pacientes con niveles de calcio iónico inferiores a 1,1 mmol/l en las primeras 24 horas del post operatorio OR: 0,5, IC (0,2-1,2) p: 0,1. Sin determinarse asociación por limitaciones del estudio, sin embargo un 29% de los pacientes con fibrilación auricular tuvieron niveles de calcio inferiores a 1,1 mmol/l en las primeras 24 horas del post operatorio, este valor aumenta a 31% cuando se analizan por separado los valores de calcio obtenidos a las 12 horas. Conclusiones. Aunque no se logró determinar asociación entre la fibrilación auricular post operatoria y las concentraciones de calcio iónico, de manera exploratoria se pudo establecer que un 29% de los pacientes con fibrilación auricular tuvieron concentraciones de calcio iónico inferiores a 1,1 mmol/l, este valor aumenta a 31% cuando se analizan los niveles de calcio iónico por separado.

Control of heart rate during thermoregulation in the heliothermic lizard Pogona barbata: importance of cholinergic and adrenergic mechanisms

During thermo regulation in the bearded dragon Pogona barbata, heart rate when heating is significantly faster than when cooling at any given body temperature (heart rate hysteresis), resulting in faster rates of heating than cooling. However, the mechanisms that control heart rate during heating and cooling are unknown. The aim of this study was to test the hypothesis that changes in cholinergic and adrenergic tone on the heart are responsible for the heart rate hysteresis during heating and cooling in P. barbata. Heating and cooling trials were conducted before and after the administration of atropine, a muscarinic antagonist, and sotalol, a beta-adrenergic antagonist. Cholinergic and beta-adrenergic blockade did not abolish the heart rate hysteresis, as the heart rate during heating was significantly faster than during cooling in all cases. Adrenergic tone was extremely high (92.3%) at the commencement of heating, and decreased to 30.7% at the end of the cooling period. Moreover, in four lizards there was an instantaneous drop in heart rate (up to 15 beats min(-1)) as the heat source was switched off, and this drop in heart rate coincided with either a drop in beta-adrenergic tone or an increase in cholinergic tone. Rates of heating were significantly faster during the cholinergic blockade, and least with a combined cholinergic and beta-adrenergic blockade. The results showed that cholinergic and beta-adrenergic systems are not the only control mechanisms acting on the heart during heating and cooling, but they do have a significant effect on heart rate and on rates of heating and cooling.

Alpha1b-adrenergic receptors control locomotor and rewarding effects of psychostimulants and opiates.

Drugs of abuse, such as psychostimulants and opiates, are generally considered as exerting their locomotor and rewarding effects through an increased dopaminergic transmission in the nucleus accumbens. Noradrenergic transmission may also be implicated because most psychostimulants increase norepinephrine (NE) release, and numerous studies have indicated interactions between noradrenergic and dopaminergic neurons through alpha1-adrenergic receptors. However, analysis of the effects of psychostimulants after either destruction of noradrenergic neurons or pharmacological blockade of alpha1-adrenergic receptors led to conflicting results. Here we show that the locomotor hyperactivities induced by d-amphetamine (1-3 mg/kg), cocaine (5-20 mg/kg), or morphine (5-10 mg/kg) in mice lacking the alpha1b subtype of adrenergic receptors were dramatically decreased when compared with wild-type littermates. Moreover, behavioral sensitizations induced by d-amphetamine (1-2 mg/kg), cocaine (5-15 mg/kg), or morphine (7.5 mg/kg) were also decreased in knock-out mice when compared with wild-type. Ruling out a neurological deficit in knock-out mice, both strains reacted similarly to novelty, to intraperitoneal saline, or to the administration of scopolamine (1 mg/kg), an anti-muscarinic agent. Finally, rewarding properties could not be observed in knock-out mice in an oral preference test (cocaine and morphine) and conditioned place preference (morphine) paradigm. Because catecholamine tissue levels, autoradiography of D1 and D2 dopaminergic receptors, and of dopamine reuptake sites and locomotor response to a D1 agonist showed that basal dopaminergic transmission was similar in knock-out and wild-type mice, our data indicate a critical role of alpha1b-adrenergic receptors and noradrenergic transmission in the vulnerability to addiction.

Catechol-binding serines of beta(2)-adrenergic receptors control the equilibrium between active and inactive receptor states.

The binding free energy for the interaction between serines 204 and 207 of the fifth transmembrane helix of the beta(2)-adrenergic receptor (beta(2)-AR) and catecholic hydroxyl (OH) groups of adrenergic agonists was analyzed using double mutant cycles. Binding affinities for catecholic and noncatecholic agonists were measured in wild-type and mutant receptors, carrying alanine replacement of the two serines (S204A, S207A beta(2)-AR), a constitutive activating mutation, or both. The free energy coupling between the losses of binding energy attributable to OH deletion from the ligand and from the receptor indicates a strong interaction (nonadditivity) as expected for a direct binding between the two sets of groups. However, we also measured a significant interaction between the deletion of OH groups from the receptor and the constitutive activating mutation. This suggests that a fraction of the decrease in agonist affinity caused by serine mutagenesis may involve a shift in the conformational equilibrium of the receptor toward the inactive state. Direct measurements using a transient transfection assay confirm this prediction. The constitutive activity of the (S204A, S207A) beta(2)-AR mutant is 50 to 60% lower than that of the wild-type beta(2)-AR. We conclude that S204 and S207 do not only provide a docking site for the agonist, but also control the equilibrium of the receptor between active (R*) and inactive (R) forms.

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.

Adrenergic mechanisms of the Kölliker-Fuse/A7 area on the control of water and sodium intake

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

Role of cholinergic and adrenergic pathways of the medial septal area in the control of water intake and renal excretion in rats

In this study, we investigated an interaction between noradrenergic and cholinergic pathways of the medial septal area (MSA) on the control of water intake and urinary electrolyte excretion by means of injection of their respective agonists. Noradrenaline (a nonspecific α-adrenergic agonist) and clonidine (an α2-adrenergic agonist), but not phenylephrine (an α1-adrenergic agonist), induced natriuresis and kaliuresis. α-Adrenergic activation had no effect on the natriuresis and kaliuresis induced by carbachol (a cholinergic agonist) and it inhibited the antinatriuresis and antikaliuresis induced by isoproterenol (a ß-adrenergic agonist). Interactions related to volume excretion are complex. α-Adrenergic activation induced a mild diuresis and inhibited the antidiuresis induced by isoproterenol, but phenylephrine combined with carbachol induced antidiuresis. The water intake induced by carbachol was inhibited by clonidine and noradrenaline, but not phenylephrine. These results show an asymmetry in the interaction between α-adrenergic and cholinergic receptors concerning water intake and electrolyte excretion. © 1992.

Peptidergic control of gastrointestinal blood flow in the estuarine crocodile, Crocodylus porosus

Peptidergic mechanisms influencing the resistance of the gastrointestinal vascular bed of the estuarine crocodile, Crocodylus porosus, were investigated. The gut was perfused in situ via the mesenteric and the celiac arteries, and the effects of different neuropeptides were tested using bolus injections. Effects on vascular resistance were recorded as changes in inflow pressures. Peptides found in sensory neurons [substance P, neurokinin A, and calcitonin gene-related peptide (CGRP)] all caused significant relaxation of the celiac vascular bed, as did vasoactive intestinal polypeptide (VIP), another well-known vasodilator. Except for VIP, the peptides also induced transitory gut contractions. Somatostatin and neuropeptide Y (NPY), which coexist in adrenergic neurons of the C. porosus, induced vasoconstriction in the celiac vascular bed without affecting the gut motility. Galanin caused vasoconstriction and occasionally activated the gut wall. To elucidate direct effects on individual vessels, the different peptides were tested on isolated ring preparations of the mesenteric and celiac arteries. Only CGRP and VIP relaxed the epinephrine-precontracted celiac artery, whereas the effects on the mesenteric artery were variable. Somatostatin and NPY did not affect the resting tonus of these vessels, but somatostatin potentiated the epinephrine-induced contraction of the celiac artery. Immunohistochemistry revealed the existence and localization of the above-mentioned peptides in nerve fibers innervating vessels of different sizes in the gut region. These data support the hypothesis of an important role for neuropeptides in the control of the vascular bed of the gastrointestinal tract in C. porosus.

Exercise training prevents beta-adrenergic hyperactivity-induced myocardial hypertrophy and lesions

Background: Sustained beta-adrenoreceptor activation promotes cardiac hypertrophy and cellular injury. Aims: To evaluate the cardioprotective effect of exercise on damage induced by beta-adrenergic hyperactivity. Methods: Male Wistar rats were randomised into four groups (n=8 per group): sedentary non-treated control (C), sedentary treated with isoproterenol 0.3 mg/kg/day administered subcutaneously for 8 days (1), exercised non-treated (E) and exercised plus isoproterenol administered during the last eight days of exercise (IE). Exercised animals ran on a treadmill for 1 h daily 6 times a week for 13 weeks. Results: Isoproterenol caused increases in left ventricle (LV) wet and dry weight/body weight ratio, LV water content and cardiomyocyte transverse diameter. Additionally, isoproterenol induced severe cellular lesions, necrosis, and apoptosis, increased collagen content and reduced capillary and fibre fractional areas. Notably, all of these abnormalities were completely prevented by exercise. Conclusion: Our data have demonstrated that complete cardioprotection is possible through exercise training; by preventing p-adrenergic hyperactivity-induced cardiac hypertrophy and structural injury. (c) 2008 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Brain monoaminergic neurons and ventilatory control in vertebrates

Monoamines (noradrenaline (NA), adrenaline (AD), dopamine (DA) and serotonin (5-HT) are key neurotransmitters that are implicated in multiple physiological and pathological brain mechanisms, including control of respiration. The monoaminergic system is known to be widely distributed in the animal kingdom, which indicates a considerable degree of phylogenetic conservation of this system amongst vertebrates. Substantial progress has been made in uncovering the participation of the brain monoamines in the breathing regulation of mammals, since they are involved in the maturation of the respiratory network as well as in the modulation of its intrinsic and synaptic properties. On the other hand, for the non-mammalian vertebrates, most of the knowledge of central monoaminergic modulation in respiratory control, which is actually very little, has emerged from studies using anuran amphibians. This article reviews the available data on the role of brain monoaminergic systems in the control of ventilation in terrestrial vertebrates. Emphasis is given to the comparative aspects of the brain noradrenergic, adrenergic, dopaminergic and serotonergic neuronal groups in breathing regulation, after first briefly considering the distribution of monoaminergic neurons in the vertebrate brain. (C) 2008 Elsevier B.V. All rights reserved.

A behavioral study of alpha-1b adrenergic receptor knockout mice: increased reaction to novelty and selectively reduced learning capacities.

Knockout mice lacking the alpha-1b adrenergic receptor were tested in behavioral experiments. Reaction to novelty was first assessed in a simple test in which the time taken by the knockout mice and their littermate controls to enter a second compartment was compared. Then the mice were tested in an open field to which unknown objects were subsequently added. Special novelty was introduced by moving one of the familiar objects to another location in the open field. Spatial behavior and memory were further studied in a homing board test, and in the water maze. The alpha-1b knockout mice showed an enhanced reactivity to new situations. They were faster to enter the new environment, covered longer paths in the open field, and spent more time exploring the new objects. They reacted like controls to modification inducing spatial novelty. In the homing board test, both the knockout mice and the control mice seemed to use a combination of distant visual and proximal olfactory cues, showing place preference only if the two types of cues were redundant. In the water maze the alpha-1b knockout mice were unable to learn the task, which was confirmed in a probe trial without platform. They were perfectly able, however, to escape in a visible platform procedure. These results confirm previous findings showing that the noradrenergic pathway is important for the modulation of behaviors such as reaction to novelty and exploration, and suggest that this is mediated, at least partly, through the alpha-1b adrenergic receptors. The lack of alpha-1b adrenergic receptors in spatial orientation does not seem important in cue-rich tasks but may interfere with orientation in situations providing distant cues only.