Mecawi A S, Lepletier A, Araujo I G, Fonseca F V, Reis L C
Department of Physiological Sciences, Biology Institute, Federal Rural University of Rio de Janeiro, BR465, Km 7, 23890-000, Seropédica, RJ, Brazil.
Exp Physiol. 2008 Aug;93(8):1002-10. doi: 10.1113/expphysiol.2008.042713. Epub 2008 Apr 25.
The present work was carried out to investigate the role of angiotensin II type 1 (AT(1)) receptors in nocturnal thirst and sodium appetite induced by classical models of osmotic and sodium depletion challenges in ovariectomized rats chronically treated with oil or oestradiol benzoate (EB, 20 microg per animal, s.c. daily). In both conditions, the animals were given saline or losartan (108 nmol per animal, i.c.v.), a selective AT(1) receptor blocker. Oestrogen therapy significantly reduced the water intake induced by water deprivation, sodium depletion produced by frusemide injected 24 h before, and s.c. acute frusemide plus captopril injection (FUROCAP protocol), with no alteration following s.c. hypertonic saline injection. In contrast, EB therapy decreased the salt intake induced by sodium depletion and FUROCAP protocols, with no alteration following water deprivation and s.c. hypertonic saline injection. Central AT(1) blockade inhibited the dipsogenic response induced by water deprivation, osmotic stimulation, chronic sodium depletion and FUROCAP protocols and inhibited the natriorexigenic response induced by sodium depletion in ovariectomized rats. Oestrogen therapy significantly attenuated the losartan-induced antidipsogenic and antinatriorexigenic actions following sodium depletion and FUROCAP protocols. These results indicate that ovariectomized rats express increased AT(1) receptor signalling related to thirst and sodium appetite responses. Oestrogen therapy and brain AT(1) receptor blockade weakened or markedly decreased the behavioural responses during the nocturnal period, a time at which brain angiotensinergic activity is expected to be more prominent. Finally, we demonstrated through different experimental protocols a clear-cut influence of oestrogenic status on the behavioural AT(1)-induced signalling response.
本研究旨在探讨1型血管紧张素II(AT(1))受体在去卵巢大鼠夜间口渴和钠食欲中的作用,这些大鼠长期接受油剂或苯甲酸雌二醇(EB,每只动物20微克,皮下注射,每日一次)治疗,并通过经典的渗透和钠耗竭挑战模型诱导口渴和钠食欲。在这两种情况下,给动物注射生理盐水或氯沙坦(每只动物108纳摩尔,脑室内注射),氯沙坦是一种选择性AT(1)受体阻滞剂。雌激素治疗显著降低了由禁水诱导的饮水量、24小时前注射速尿产生的钠耗竭以及皮下注射急性速尿加卡托普利注射(FUROCAP方案)诱导的饮水量,而皮下注射高渗盐水后饮水量没有改变。相比之下,EB治疗降低了由钠耗竭和FUROCAP方案诱导的盐摄入量,而禁水和皮下注射高渗盐水后盐摄入量没有改变。中枢AT(1)受体阻断抑制了去卵巢大鼠由禁水、渗透刺激、慢性钠耗竭和FUROCAP方案诱导的饮水反应,并抑制了由钠耗竭诱导的钠食欲反应。雌激素治疗显著减弱了氯沙坦在钠耗竭和FUROCAP方案后诱导的抗饮水和抗钠食欲作用。这些结果表明,去卵巢大鼠表达了与口渴和钠食欲反应相关的AT(1)受体信号增加。雌激素治疗和脑AT(1)受体阻断减弱或显著降低了夜间的行为反应,而夜间脑内血管紧张素能活性预计更为突出。最后,我们通过不同的实验方案证明了雌激素状态对行为性AT(1)诱导的信号反应有明显影响。