RESUMEN
OBJECTIVE: In physiological conditions, renin-angiotensin-aldosterone (RAA) axis is under continuous tonic inhibition by dopamine. The aim of this study was to evaluate the relationship of nontumoural hyperprolactinemia with the activity of adrenocortical and RAA axis, before and after administration of bromocriptine. DESIGN: Twenty women with nontumoural hyperprolactinemia and 20 healthy women matched for body mass index and age were recruited in this study. All participants were placed on fixed salt intake for 2 weeks before the experiments. The study was conducted in three phases. In phase I, the participants received an intravenous infusion of angiotensin II in three consecutive doses of 2, 4 and 6 ng/kg BW changed every 30 min. In phase II, the patients were started on bromocriptine in gradually increasing doses of 1.25, 2.5, 5, 7.5 and 10 mg/day for 10 weeks. In phase III, the protocol of phase I was repeated in the patient group. Circulating levels of cortisol, plasma renin activity (PRA), aldosterone and prolactin were assayed. RESULTS: Baseline values of prolactin, and PRA (2.6±0.18 nM vs 0.45±0.05 nM P<0.001 and 142.2±14.4 vs 30.7±2.7 pM/h, P<0.001, respectively) but not aldosterone (P=0.081) were significantly higher in the patient group. The angiotensin infusion test induced a significantly greater response in the patient group. Administration of the dopamine agonist restored the basal levels and diminished the response to angiotensin infusion for all the parameters tested. No change in the blood pressure was recorded. CONCLUSIONS: Our study demonstrates that in nontumoural hyperprolactinemia there is an increased reactivity of renin-angiotensin-aldosterone (RAA) axis that is almost completely restored after treatment with a dopamine agonist.
Asunto(s)
Hiperprolactinemia/fisiopatología , Sistema Renina-Angiotensina/fisiología , Adulto , Aldosterona/sangre , Angiotensina II/administración & dosificación , Angiotensina II/farmacología , Bromocriptina/administración & dosificación , Bromocriptina/farmacología , Creatinina/sangre , Creatinina/orina , Agonistas de Dopamina/administración & dosificación , Agonistas de Dopamina/farmacología , Femenino , Humanos , Hidrocortisona/sangre , Hiperprolactinemia/sangre , Hiperprolactinemia/orina , Prolactina/sangre , Radioinmunoensayo , Renina/sangre , Sistema Renina-Angiotensina/efectos de los fármacos , Sodio/sangre , Sodio/orinaRESUMEN
The prevalence of obesity has increased dramatically during the last thirty years in western countries with severe complications for health and economy. Obesity is the outcome of the strong interplay between genetic and environmental factors and is therefore widely expected that the discovery of the many genetic factors underlying the heritable risk of obesity will contribute critically to our basic knowledge of the disease etiopathogenesis and the identification of new targets for therapeutic intervention. The aim of the present study was to assess the genetic contribution of known polymorphisms in two genes that are linked to the pathogenetic mechanism of obesity. Analysis of vitamin D receptor (VDR) TaqI (rs731236; T/C) and fat mass and obesity-associated (FTO) (rs9939609; A/T) [corrected] polymorphisms in 82 obesity subjects and 102 controls showed significant association for VDR TaqI 'T' allele and obesity (OR: 2.07; 1.123-3.816; P=0.019), contributing to an elevated BMI of 3kg/m(2) per risk allele. No association was observed for the FTO polymorphism. These results further support a role for VDR as risk factor for obesity and suggest its further validation in larger independent populations as well as highlight a target for functional analysis towards therapeutic intervention in obese individuals.