Thyroid hormone and adrenergic signaling in the heart

A ação do hormônio tireoideano tem consequências profundas no sistema cardiovascular, as quais variam desde fibrilação atrial ao colapso hemodinâmico. Há muito sabe-se que os sinais e sintomas cardiovasculares detectados na tireotoxicose assemelham-se aos observados em estados hiper-adrenérgicos. Entretanto, as concentrações séricas de catecolaminas em pacientes com tireotoxicose são tipicamente normais ou mesmo baixas, sugerindo um aumento na responsividade adrenérgica no coração tireotóxico. A despeito de várias décadas de trabalho, a questão sobre se o hormônio tireoideano aumenta a responsividade adrenérgica é ainda controversa. Nesta revisão, nós consideramos os motivos que alimentam esta controvérsia, focalizando na complexidade da cascata de sinalização adrenérgica.

Utilidad de la clonidina por vía peridural en anestesiología / Utility of the clonidine for via peridural in anesthesiology

Los fármacos agonistas adrenérgicos alfa-2 se han utilizado en la práctica clínica desde hace varios años por sus propiedades simpaticolíticas benéficas en el tratamiento de la hipertensión principalmente. La clonidina, en específico, ha cumplido bien este cometido. Pero, además, se han identificado otras propiedades de la clonidina que la hacen útil para la práctica de la anestesiología. Esto es, la analgesia, la sedación, la ansiolisis y también la simpaticóolisis. Estos efectos los consigue actuando básicamente sobre el subtipo alfa-2a. Los usos en la anestesiología abarcan los periodos pre, trans y posoperatorio; actuando como buenos medicamentos preanestésicos, disminuyendo requerimientos anestésicos de otros fármacos y, por lo tanto, facilitando la emergencia y recuperación de la anestesia. Además, su uso en el manejo del dolor posoperatorio ha cobrado una importancia significativa, observándose que la vía espinal es la que mayores ventajas y beneficios ofrece sobre las demás vías y rutas de administración, viéndose limitada únicamente por sus efectos colaterales como son hipotensión, bradicardia y sedación, pero que no producen inestabilidad hemodinámica que contraindique, per se, su uso.

Important recent advances in cardiovascular adrenergic mechanisms

Five sub-areas were taken into consideration: Adrenoceptor subclassification: Presently, 10 different adrenoceptor subtypes have been characterized by pharmacological and molecular biology studies: Ó1A-, Ó1B-, Ó1D-, Ó2A/D, Ó2B-, Ó2C-, ß1-, ß2-, ß3- and ß4-adrenoceptors. Intracellular signaling: the adrenoceptors are members of a large superfamily of receptors linked to guanine-nucleotide proteins (G proteins), Ó1-adrenoceptors are coupled to Gq proteins and activate phospholipases, especially phospholipase Cß, Ó2-adrenoceptors are coupled to G1 proteins and inhibit adenylyl cyclase and in some tissues regulate potassium and calcium channels. Both ß1 and ß2-adrenoceptors are preferentially coupled to adenylyl cyclase through GS proteins and ß3-adrenoceptors appear to be coupled to K+ channel through a pertussis toxin-sensitive G1 protein. ß4-Adrenoceptors appear to be coupled positively to a cyclic AMP-dependent cascade and can undergo desensitization. Influence of maturation and ageing: From birth to old age important changes occur in animal models as in humans at the receptor level, neurotransmitter process and catecholamine disposition. In general terms, one can say that maturation is associated with a gradual increase of adrenergic influence, while ageing is associated with a reduction in the role of the adrenergic system on the regulation of physiologic processes. Cotransmission: ATP and the neuropeptide Y are cotransmitters with noradrenaline. While noradrenaline is the main transmitter in vascular tissues, ATP has functional relevance in some vessels and neuropeptide Y is mainly a modulator of noradrenaline release; it seems that it has an increased role under pathophysiological conditions like ischemia. Role of endothelium on noradrenaline release: Many substances produced by the endotelium or acting through the endothelium are able to influence noradrenaline release from sympathetic nerve varicosities of the blood vessel wall: some of them, like bradykinin and angiotensin II, exert a facilitatory, while others like NO and endothelin have an inhibitory effect on noradrenaline release evoked electrical nerve stimulation.

Quantitative receptor radioautography in the study of receptor-receptor interactions in the nucleus tractus solitarii

The nucleus tractus solitarii (NTS) in the dorsomedial medulla comprises a wide range of neuropeptides and biogenic amines. Several of them are related to mechanism of central blood pressure control. Angiotensin II (Ang II), neuropeptide Y (NPY) and noradrenaline (NA) are found in the NTS cells, as well as their receptors. Based on this observation we have evaluated the modulatory effect of these peptide receptors on alpha2-adrenoceptors in the NTS. Using quantitative recptor radioautography, we observed that NPY and Ang II receptors decreased the affinity of alpha1-adrenoceptors for their agonists in the NTS of the rat. Cardiovascular experiments agreed with the in vitro data. Coinjection of a threshold dose of Ang II of the NPY agonists together with an ED50 dose of adrenergic agonists such as NA, adrenaline and clonidine counteracted the depressor effect produced by the alpha2-agonist in the NTS. The results provide evidence for the existence of an antagonistic interaction between Ang II AT1 receptors and NPY receptor subtypes with the alpha2-adrenoceptors in the NTS. This receptor interaction may reduce the transduction over the alpha2-adrenoceptors which can be important in central cardiovascular regulation and in the development of hypertension.

Control of melanosome movements in isolated skin melanophores of a catfish Clarias batrachus (Linn.).

Adrenergic and cholinergic receptors have been studied in isolated skin melanophores of a catfish Clarias batrachus. Catecholamines induced a strong aggregatory effect on the melanophores. Melanosome aggregation induced by adrenaline and noradrenaline was partially blocked by alpha adrenergic receptor blockers and a beta receptor blocker. Cholinomimetic drugs aroused a significant dispersion of melanophroes. Atropine effectively blocked the dispersal, responses of melanophores to acetylcholine and carbachol, while, hexamethonium blocked the nocotine induced dispersal responses of the melanophores.

Sistema adrenérgico en los residentes de grandes alturas / Adrenergic system at high altitude population

Heart rate (FC) response to perfusion with isoprenaline is decreased in sealevel natives on expuser to high altitude hypoxia. Since noredraline concentration in plasma is elevated under these condition as phenomenon of downregulation of the betareceptors (BAR) cuold be evoked. For the fisrt time, this aspect was explored in a population native from and residing at 3600 m consisting of normocythemics (HAN) and polycythemics (HAP). the results were compared to those obtained from a sealevel population, exmined in normoxia (SLN) at 4800 m (J. Appl. Physiol. 65:1975-61, 1988). The dose necessary to increase FC by 25 beats per min (125) was identical for HAN and HAP as well as SLN. This iondicates that the chronotropic responses is igual in the two populations when they are studied in their habitual environment; to the contrary, this response is diminished in SLH, thus correlating to the phenomenon of downregulation.

Renal water handling evaluated by lithium clearance following adrenergic and cholinergic stimulation of the lateral hypothalamic area

Male Wistar rats weighing 230-3--g were used to characterize the participation of adrenerg and cholinergic receptors of the lateral hypothalamic area (LHA) in the control of renal water excretion. Since stimulation of adrenergic or cholinergic receptors has no effect on glomerular filtration rate, the antidiuresis and significant delay in urinary flow observed after lateral hypothalamic stimulation with carbachol (CCh) (0.036 ñ 0.005 to o.019 ñ 0.003 µlmin-1 100g body weight-1) and noradrenaline (Nad) (0.024 ñ 0.005 to 0.025 ñ 0.004 µl min-1 100g body weight-1) are secondary to an increase in distal tubular fluid reabsorption (DFR). Data are reported as means ñ SEM for ten rats each group. Tubular water measured by lithim clearance demonstrated that LHA stimulation with CCh (2.8 nmol in 1 µl) and Nad (30.0 nmol in µl) leads to a significant reduction in proximal water reabsorption with CCh, 93.3 ñ 2.6 to 85.4 ñ 1.4%; Nad, 92.7 ñ0.9 to 88.6 ñ 1.3%), with a simultaneous and significant incrase in fluid reabsorption along the post-proximal nephrom segments when compared to control (CNa) (CCh, 6.7 ñ 0.7 to 14.5 ñ 1.1%; Nad 8.2 ñ 0.8 to 11.4 ñ 1.6%) These effects are blocked by muscarinic (atropine, 5 nmol in 1 µl) and alpha-1 adrenoceptors (prazosin, 4 nmol in 1 µl) antagonists. The results indicate the effective participation of the post-proximal nephron in the antidiuresis occurring after cholinergic and adrenergic LHA stimulation

Sistema beta-adrenérgico. I. Seu papel na homeostasia materna / Beta-adrenergic system. I. Its role in maternal homeostasis

Os autores revêem o conceito de receptores adrenérgicos e estudam o tono basal do sistema nervoso autônomo. Avaliam minudentemente os efeitos da estimulaçäo e do bloqueio beta-adrenérgico sobre os sistemas cardiovascular, pulmonar, renal e uterino, bem como sobre as funçöes metabólicas. Enfatizam as diferenças entre as respostas do organismo grávido e näo-grávido. Alertam obstretas e perinatólogos para a grande variedade de açöes fisiofamacológicos do sistema beta-adrenérgico, fato que exige cuidado quando da utilizaçäo de agonistas e antagonistas deste sistema na gravidez

Adrenergic receptors in the hypothalamus concerned with control of arterial blood pressure: elicited by electrical and chemical stimulation.

The study was made with the help of a chemitrode placed in various areas of the hypothalamus by the stereotaxic technique, for electrical and chemical stimulation (noradrenaline or isoprenaline) before and after microinjection of respective blockers (phenoxybenzamine or practalol). The results indicated the presence of both alpha and beta-adrenoreceptors in the anterior and dorsomedial hypothalamus producing a depressor response, and, the presence of alpha adrenoreceptors in the posterior and lateral hypothalamus producing a pressor response.