RESUMO
We have demonstrated that acute third ventricle injections of lead acetate (PbAc) exert a powerful antidipsogenic effect and induce a significant increase in renal sodium excretion. In the present study we confirm the antidipsogenic effect of lead and demonstrate that central administration of this metal, in minute amounts, significantly reduces salt intake both during dehydration and after central angiotensinergic stimulation. Adult male Wistar rats had the third ventricle cannulated seven days before the experiments. During this period they had free access to distilled water and hypertonic saline solution (1.5%). After a 24-h period of fluid deprivation, experimental animals received third ventricle injections of PbAc (0.3, N = 8 and 3.0 nmol/rat, N = 14) while controls received sodium acetate (NaAc; 3.0 nmol/rat, N = 10). Rats treated with PbAc at the highest dose showed a significant reduction (P<0.05) both in water and hypertonic saline intake when compared to controls. When the effect of lead administration on angiotensin II-induced water and salt intake was studied, normohydrated animals received third ventricle injections of angiotensin II (9.6 nmol/rat) after pretreatment with 3.0 nmol/rat of PbAc (experimental group, N = 10) or NaAc (controls, N = 8). The group pretreated with PbAc presented a significant reduction (P<0.05) in both water and salt intake compared to controls. Thus, this study confirms the antidipsogenic effect of central lead injections and demonstrates that the presence of lead in the brain exerts a significant inhibition of sodium appetite.
Assuntos
Angiotensinas/farmacologia , Apetite/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Compostos Organometálicos/administração & dosagem , Sódio na Dieta/administração & dosagem , Animais , Líquidos Corporais/efeitos dos fármacos , Injeções Intraventriculares , Masculino , Compostos Organometálicos/farmacologia , Ratos , Ratos WistarRESUMO
We investigated the genesis of the hypertensive response to acute (45 min) aortic constriction in two models of chronic vasopressin (AVP) deficiency, i.e., Brattleboro strain and median eminence lesioned (MEL) Wistar rats. The same degree of partial aortic constriction, with a pneumatic cuff placed around the abdominal aorta, yielded a sudden and maintained increase in carotid pressure to the same extent in Brattleboro, MEL and sham-MEL rats. Blockage of AVP V1 receptors with d(CH2)5Tyr[Me]AVP did not affect the hypertensive response of Brattleboro or MEL rats, but gradually blunted the response of sham-MEL rats. Blockage of angiotensin II receptors with saralasin blunted the hypertensive response of the AVP-deficient subjects throughout the experiment, but only delayed (5-15 min) the onset of hypertension in sham-MEL rats. Simultaneous blockage of AVP and angiotensin II blunted the hypertensive response of sham-MEL and AVP-deficient rats throughout the experiment. These data demonstrate that when one vasoactive system is chronically absent, as is the case for AVP in Brattleboro and MEL rats, the renin-angiotensin system plays the major role in the pathophysiology of acute aortic coarctation hypertension.
Assuntos
Coartação Aórtica/complicações , Arginina Vasopressina/deficiência , Hipertensão/etiologia , Antagonistas de Receptores de Angiotensina , Animais , Antagonistas dos Receptores de Hormônios Antidiuréticos , Coartação Aórtica/fisiopatologia , Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/farmacologia , Arginina Vasopressina/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Doença Crônica , Feminino , Antagonistas de Hormônios/farmacologia , Hipertensão/fisiopatologia , Masculino , Eminência Mediana/lesões , Ratos , Ratos Brattleboro , Ratos Wistar , Sistema Renina-Angiotensina/fisiologia , Saralasina/farmacologiaRESUMO
There are now more than 50 studies concerning neuroleptic blood levels and clinical outcome relationships. Haloperidol, the most studied, is the only antipsychotic permitting some conclusions. A number of authors suggest that the striking lack of agreement between different studies results from heterogeneity of their quality. Here, we have used a scoring system for assessing the quality of those studies. According to this system, none (0/14) of the studies having a score < 0.60 was able to show a therapeutic window, as compared to 53% (10/19) of those having a score > or = 0.60 (p = 0.002, Fisher exact test). Also, the studies able to identify the presence of a therapeutic window during haloperidol treatment were those having sample size > 20 (p = 0.06) and those whose patients were treated with fixed doses (p = 0.02). The diagnosis of schizophrenia in the studies seems not to be an exclusive condition, as compared with those also including schizophreniform and schizoaffective disorders (p = 0.12). Our qualitative analysis of haloperidol blood level publications seem to indicate that an upper limit may exist for haloperidol efficacy; values above this limit seem not to provide any supplementary clinical improvement and may even reduce therapeutic effect.
Assuntos
Antipsicóticos/sangue , Antipsicóticos/uso terapêutico , Haloperidol/sangue , Haloperidol/uso terapêutico , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Relação Dose-Resposta a Droga , Humanos , Resultado do TratamentoRESUMO
The influence of the central adrenergic system on basal prolactin secretion was investigated in the rat. Several selective adrenoceptor blockers were centrally administered and their effects on prolactin secretion were observed. Blockade of beta-1 receptors by practolol, beta-2 receptors by IPS 339 and alpha-2 receptors by DG-5128 did not modify basal prolactin secretion, but alpha-1 adrenoceptor blockade by prazosin strongly enhanced prolactin plasma levels. These findings suggest that noradrenergic pathways in the central nervous system exert inhibitory tone on basal prolactin secretion, and that this effect seems to be mediated by alpha-1 adrenoceptors.