ABSTRACT
It has been widely established that dopamine and its agonists exect an import role in the regulation of the cardiovascular, renal hormonal systems, acting through adrenergic and beta-adrenergic systems. There are several DA-2 agonists such as bromocriptine pergolide, lisuride, and largotrile, which belong to the ergolin family and act both at central and peropheral levels-inhibiting norepinephrine release, which produces a decrease of arterial pressure and, in some cases, such as with bromocriptine and pergolide, a decrease in the heart rate. From a therapeutic viewpoint, the above mentioned DA-2 agonists are widely used for treating Parkinso's disease; these agonists act at the level of DA-2 receptors located in the nigrostriatal system. Bromocriptine and the other mentioned agonists DA-2 are used in the treatment of hyperprolatinemia and in pivitary tumors, since they decrease prolactin secretion and reduce the size of the tumor acting through inhibitory DA-2 receptors located in the tuberoinfuldibolar system. Similarly, there are Also DA-1 agonists such fenoldopam (selective) and piribedil non selective) which activate peripheral receptors, producing, a reduction of peripheral resistance and renal vascular resistance and an renal vascular resistance and an increase of renal blood flow. All these effects produce a decrease in arterial pressure and a reflex hearth rate increase. Fenoldopam in used in the treatment of arterial hypertensión, renal failure and heart failure. This agonist exerts its action at the level of the DA-1 receptors located in peripheral and renal resistance vessels (which leads to an increase use in renal blood flow and a decrease pressure). Among the selecttive antagonists of DA-2 receptors, we can mention metoclopramide and domperidone. Both antagonists produce a decrease in the hypotensor response of treatment of schizophrenia; it acts by activating DA-1 and DA-4 recepts located at the hypothalamus, olfactory bulb, and frontal cortex
Subject(s)
Humans , Male , Female , Dopamine/pharmacology , Dopamine/therapeutic useABSTRACT
This study was conduced in normotensive and hypertensive patients at the Vargas Hospital of Caracas. Normotensive subjects received, in a crossover fashion, placebo, metoclopramide or domperidone, 40 mg of each drug daily for one week. The first group of patients under placebo for one(1) week received a single 2.5 mg oral dose bromocriptine (Br). The second group of patients received 30 mg of metoclopramide (MTC) daily (divided in 3 doses) for week. At the end of period a single dose of 2.5 mg of Br was given to each patient . The third group received domperidone (DOMP) during one week at 30 mg/daily dose to eight hypertesive patients and then a single dose of 2.5 mg Br. Cardiovascular and biochemical parameters including arterial pressure, heart rate, plasma renin activity, and plasma aldosterone concentration were evaluated during the 6 hour period before and after the administration of Br. Neither DOMP nor MTC modified significantly blood presure and heart rate in normotensive subjects. Br reduced both systolic and diastolic arterial pressure in hypertensive subjects. The peak of antihypertensive effect appeared 3 hours after drug administration, but reduction of arterial pressure lasted aproximately 6 hours. At the same time Br reduced plasma aldosterone levels and plasma renin activity. MTC and DOMP reversed the antihypertensive effct or Br and its effect on aldosterone levels and plasma renin activity. We conclude from these findings that Br acts as an antihypertensive agent at peripheral and central levels by stimulating DA2 receptors, which are involved in the aldosterone and renin secretion
Subject(s)
Humans , Male , Female , Bromocriptine , Domperidone , Domperidone/blood , Hypertension/therapy , Metoclopramide , Metoclopramide/blood , PatientsABSTRACT
Está ampliamente establecido que la dopamina y sus agonistas ejercen un papel importante en la regulación del sistema cardiovascular, renal y hormonal, actuando a través de los receptores-adrenérgicos y ß adrenérgicos. Existen varios agonistas DA-2 tales como bromocriptina, el pergolide, el lisuride pertenece a la familia de las ergolinas que actúan tanto a nivel central como a nivel periférico, inhibiendo la liberación de norepinefrina lo cual produce una disminución de la presión arterial y en algunos casos tales como la bromocriptina y el pergolide, causan una disminución de la frecuencia cardíaca. Desde el punto de vista terapéutico, los agonistas DA-2 antes mencionados se utilizan ampliamente en el tratamiento de la enfermedad de Parkinson, estos agonistas actúan a nivel de receptores DA2 situados en el sistema nigroestríado. La bromocriptina y los otros agonistas DA2 mencionados, se utilizan en el tratamiento de la hiperprolactinemia y en tumores hipofisarios, estos agonistas disminuyen la secreción de prolactina y reducen el tamaño del tumor actuando a través de receptores DA2 inhibidores situados en el sistema tuberoinfundibular. De manera similar también existen agonistas DA-1 como el fenoldopam (selectivo) y el piribedil (no selectivo) estos agonistas actúan los receptores periféricos causando una reducción de la resistencia periférica, de la resistencia vascular renal y un aumento del flujo sanguíneo renal. Todos estos efectos traen como consecuencia un descenso en la presión arterial y un aumento reflejo en la frecuencia cardíaca. El fenoldopam se utiliza en el tratamiento de la hipertensión arterial, insufiencia renal e insuficiencia cardíaca este agonista ejerce su acción a nivel de la de los receptores DA-1 localizados en las arterias periféricas y renales reduciendo la resistencia periférica, y la resistencia renal, esto trae como consecuencia un aumento del flujo sanguíneo renal y una disminución de la presión arterial. Dentro de los antagonsitas de los receptores DA-2 selectivos podemos mencionar la metoclopramida y la domperidona. ambos antagonistas causan disminución de la respuesta depresora de la dopamina. Se utiliza ampliamente en el tratamiento de desórdenes gastrointestinales. El antagonista específico de los receptores DA1 es la clozapina y el SCH23390. La clozapina se utiliza ampliamente en el tratamiento de la esquizofrenia, actúa activando los receptores DA1 y DA4 situados en el hipotálamo bulbo olfatorio y corteza frontal