RESUMO
We investigated the effect of inter-renal aortic coarctation on the function and expression of vascular α(1A)- and α(1D)-adrenoceptors and plasma angiotensin II (ATII) in rats. Male Wistar rats, either sham operated (SO), or with aortic coarctation for 7 (AC7) and 14 days (AC14) were used for agonist-induced pressor responses in vehicle (physiological saline)- and antagonist-treated anesthetized animals, immunoblot analysis (α(1A)- and α(1D)-adrenoceptor in aorta and caudal arteries), and immunoassay (plasma ATII). The α(1D)-adrenoceptor antagonist, BMY-7378 (BMY) blocked noradrenaline-induced responses in the order SO > AC7 â« AC14; in contrast, the α(1A)-adrenoceptor antagonist RS-100329 (RS), produced a marginal shift to the right of the dose-response curve to noradrenaline, along with a strong decrease of the maximum pressor effect in the order SO > AC7 = AC14. The potency of the α(1A)-adrenoceptor agonist A-61603 increased in rats with AC14, and responses were inhibited by RS in the order AC14 > AC7 > SO. In aorta, α(1D)-adrenoceptor protein increased in AC7 and decreased in AC14; α(1A)-adrenoreceptor protein increased in the caudal artery of AC7 and returned to control values in AC14. Plasma ATII increased in AC7 and AC14, compared with SO rats. These results suggest an early and direct relationship between ATII and α(1D)-adrenoreceptors in the development of hypertension in this experimental model.
Assuntos
Coartação Aórtica/metabolismo , Coartação Aórtica/fisiopatologia , Hipertensão Renovascular/metabolismo , Hipertensão Renovascular/fisiopatologia , Receptores Adrenérgicos alfa 1/biossíntese , Receptores Adrenérgicos alfa 1/fisiologia , Agonistas de Receptores Adrenérgicos alfa 1/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Angiotensina II/sangue , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/fisiologia , Coartação Aórtica/sangue , Coartação Aórtica/complicações , Relação Dose-Resposta a Droga , Hipertensão Renovascular/sangue , Hipertensão Renovascular/complicações , Imidazóis/farmacologia , Masculino , Norepinefrina/antagonistas & inibidores , Norepinefrina/farmacologia , Piperazinas/farmacologia , Ratos , Ratos Wistar , Tetra-Hidronaftalenos/farmacologia , Timina/farmacologia , Timina/fisiologiaRESUMO
The effect of NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimido]-butyl] piperazine), described as a mixed 5-HT(1A) receptor agonist/antagonist, on cardiovascular function was studied. The i.v. injection of NAN-190 (1-300 micro/kg) dose-dependently decreased blood pressure (p<0.001), while heart rate was not significantly modified compared to saline-treated, anaesthetized adult rats. WAY 100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide), a highly selective 5-HT(1A) receptor antagonist, increased NAN-190-induced hypotension (p<0.05). In the pithed rat NAN-190 displaced the phenylephrine dose-pressor response curve to the right; ED(50) values were: approximately 14, 20, 40 and 270 microg/kg for saline and NAN-190 (1, 10 and 100 microg/kg, respectively); similar ED(50) values were obtained with prazosin ( approximately 20, 69 and 358 microg/kg for 1, 10 and 100 microg/kg of prazosin, respectively). NAN-190 shifted to the right the concentration-response curves to phenylephrine in rat tail artery (alpha(1A)-adrenoceptors), in rabbit aorta (alpha(1B)-adrenoceptors) and in rat aorta (alpha(1D)-adrenoceptors), with pA(2) values of 9.47, 9.02 and 9.99; while Schild slopes were -0.78, -1.13 and -0.90, respectively (not significantly different from unity). The results show that NAN-190 induced hypotension in the anaesthetized, adult rat and suggest that this effect could be explained by antagonism of vascular alpha(1)-adrenoceptors.
Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1 , Hipotensão/induzido quimicamente , Piperazinas/farmacologia , Antagonistas da Serotonina/farmacologia , Animais , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Piperazinas/efeitos adversos , Coelhos , Ratos , Ratos Wistar , Antagonistas da Serotonina/efeitos adversos , Vasoconstrição/efeitos dos fármacosRESUMO
Las fisuras labiopalatinas son defectos anatomofuncionales que disminuyen las posibilidades de vida del recién nacido que las padece. Son una de las malformaciones congénitas más frecuentes en los seres humanos.Los niños que presentan estas anomalías necesitan mucha asistencia médica interdisciplinaria durante sus primeros años.De acuerdo al total de nacimientos vivos en el Hospital Central Militar, del 1§ de diciembre de 1997 al 31 de diciembre de 1998, que fue de 5,188, se presentaron 11 casos con algún tipo de fisura labiopalatina, siendo su incidencia entonces de 1:472.Nueve afectaron al sexo masculino y dos el femenino. El labio y paladar fisurado en cualquiera de sus variantes, se presentó con mayor frecuencia (7 casos). Predominó la fisura unilateral izquierda completa o incompleta (9 casos). Ocho fueron embarazos deseados y tres no deseados.La mayoría de casos se manejaron con obturador palatino de acrílico, para mejorar su alimentación principalmente y 5 de éstos, se manejaron además, con reposicionador elástico de premaxila o ®bigotera¼ (gorro de tela y resorte elástico) como tratamiento prequirúrgico.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Obturadores Palatinos/tendências , Fissura Palatina/cirurgia , Fissura Palatina/reabilitação , Fissura Palatina/epidemiologia , Anormalidades da Boca/diagnósticoRESUMO
Heterogenic of vascular Ó1D-adrenoceptor subtypes has been revealed by pharmacological and molecular biology studies (i.e., Ó1A- , Ó1B- , and Ó1D-adrenoceptors). The Ó1D-adrenoceptor subtype is predominantly involved in the contraction of a variety of vessels and its role in the control of blood pressure has been suggested, a phenomenon probably related to aging. Recent advances in the use of young pre-hypertensive rats and adult spontaneously hypertensive ratas with one kidney and Grollman-type renal hypertension suggest vascular Ó1D-adrenoceptor involvement in the increased blood pressure. The possible role of Ó1D-adrenoceptors in the genesis/maintenance of hypertension is discussed in this review
Assuntos
Animais , Ratos , Hipertensão/fisiopatologia , Vasos Sanguíneos/fisiopatologiaRESUMO
La espiroxatrina, un ligando 5-HT1A, tiene muy baja afinidad por los sitios de unión Ó1-adrenérgicos y una afinidad relativamente alta por los sitios Ó2. No obstante, estudios funcionales recientes indican que la espiroxatrina es un potente antagonista de los receptores adrenérgicos a1 que median la contracción de la aorta de rata in vitro. Tomando en consideración las notables diferencias en la interacción de los fármacos con los receptores adrenérgicos Ó presentes en los diferentes modelos experimentales, el presente estudio fue diseñado para analizar las propiedades antagonistas Ó-adrenérgicas de la espiroxatrina en la rata descerebrada y desmedulada montada para el registro de la presión arterial. La norepinefrina y los agonistas adrenérgicos Ó1 y Ó2 metoxamina y clonidina, respectivamente, produjeron incrementos de la presión arterial en forma dependiente de la dosis. La espiroxitrina (1 mg/kg, i.v.) produjo un desplazamiento significativo de las curvas dosis-respuesta a los tres agonistas. La magnitud de dicho desplazamiento fue similar en los tres casos. Los resultados presentes sugieren que, aunque la espiroxatrina presenta propiedades antiadrenérgicas Ó1 y Ó2 en el modelo in vivo utilizado en este estudio, su potencia antagonista no parece corresponder con la encontrada en la aorta de rata. La posible participación de subtipo del receptor adrenérgico Ó1 es discutida
Assuntos
Animais , Ratos , Clonidina/farmacocinética , Metoxamina/farmacocinética , Norepinefrina/farmacocinética , Receptores Adrenérgicos/antagonistas & inibidores , Simpatolíticos/antagonistas & inibidores , Espiperona/análogos & derivadosRESUMO
The aim of this study was to provide further evidence about the participation of Ó1-adrenoceptors in the vascular responses elicited by impsapirone. This 5-HT 1A agonist displayed vasodilator activity only when aortic rings were precontracted by Ó-adrenergic compounds. The relaxant effect was particulary evident when rings were precontracted with methoxamine (selective Ó1A-adrenergic agonist).On the other hand, ipsapirone but chloroethylclonidine (selective Ó1B-adrenergic antagonist), clearly displaced norepinephrine and methoxaminevasocontractile concentration-response curves to the right. Fanally, ipsapirone protected the Ó-adrenoceptors from the irreversible blockade provoked by phenoxybenzamine, as judged by thenorepinephrine contraction and stimulated phosphatidylinositil labeling. Accordingly the relaxant effect elicited by ipsapirone in aortic rings precontracted with Ó-adrenergic agonists and the protective action against blockade by phenoxybenzamine shown by this agent are proof of its ability to occupy Ó1-adrenoceptors. Specifically, Ó1A-adrenergic receptors seem to be involved in ipsapirone vascular effects, since this agent selectively relaxed aortic preparation precontracted with methoxamine and unlike chloroethylclonidine, clearly inhibited the contractile effect of this agonist. In summary, the present findings can be explained by accepting that ipsapirone may act as an antagonist at Ó1A-adrenoceptors
Assuntos
Animais , Coelhos , Norepinefrina/farmacologia , Fenoxibenzamina/farmacologia , Receptores Adrenérgicos alfa/farmacologiaRESUMO
El síndrome de Fryns es un padecimiento genéticamente determinado, con herencia autosómica recesiva, por lo general mortal y con expresividad variable, manifestado por deformidades congénitas múltiples, como anomalías craneofaciales, hernia diafragmática, hipoplasia pulmonar, anomalías distales de los miembros y malformaciones diversas de los sistemas cardiovascular, gastrointestinal, genitourinario y del sistema nervioso central. La relación frecuente con la ocurrencia familiar, el principio temprano de polihidramnios, un parto prematuro y la mortalidad perinatal sugiere fuertemente el diagnóstico. Presentamos un caso que tenía los signos cardinales del síndrome de frys, además de otras anomalías no descritas previamente.