Kraly F S, Tribuzio R A, Kim Y M, Keefe M E, Braun C J, Newman B H
Department of Psychology, Colgate University, Hamilton, NY 13346, USA.
Physiol Behav. 1995 Dec;58(6):1099-109. doi: 10.1016/0031-9384(95)02049-7.
A role for endogenous angiotensin II and its AT1 and AT2 receptor subtypes for mediating drinking elicited by eating was examined in adult male Sprague-Dawley rats. The ability of pharmacological antagonism of AT1 and/or AT2 receptors to abolish drinking elicited by exogenous angiotensin II was established first. The s.c. injection of the AT1 antagonist losartan (DuP 753) was sufficient to abolish drinking elicited by s.c. angiotensin II. The ICV injection (through a surgically implanted chronic cannula) of losartan inhibited drinking elicited by ICV angiotensin II; the combined ICV injection of losartan plus the AT2 antagonist PD123319 was sufficient to abolish drinking elicited by ICV angiotensin II. For rats drinking and eating after 24-h food deprivation, s.c. losartan plus PD123319 inhibited water to food ratio, but ICV losartan and/or PD123319 failed to inhibit food-related drinking. For nondeprived rats eating a small cracker, s.c. losartan and/or PD123319 attenuated water intake, but only ICV losartan produced statistically significant inhibition of drinking elicited by ingestion of cracker. The IG infusion (through a surgically implanted gastric catheter) of 2 ml 600 or 900 mOsm/kg NaCl, a treatment that is subthreshold for increase in systemic plasma osmolality at the initiation of drinking, elicited drinking that was attenuated by s.c. losartan and/or PD123319 and attenuated by ICV losartan only. The IG infusion of 2 ml 1800 mOsm/kg NaCl, a treatment that is above threshold for increase in systemic plasma osmolality at the initiation of drinking, elicited drinking that was not inhibited by S or ICV losartan and/or PD123319. These results demonstrate that peripheral AT1 and AT2 and central AT1 receptors for angiotensin II contribute to drinking elicited by eating and the gastrointestinal osmotic consequences of eating. These findings extend the evidence demonstrating a renal renin-angiotensin contribution to food-related drinking in rats.
在成年雄性斯普拉格-道利大鼠中，研究了内源性血管紧张素II及其AT1和AT2受体亚型在介导进食引起的饮水方面的作用。首先确定了AT1和/或AT2受体的药理学拮抗作用消除外源性血管紧张素II引起的饮水的能力。皮下注射AT1拮抗剂氯沙坦（DuP 753）足以消除皮下注射血管紧张素II引起的饮水。通过手术植入的慢性套管进行脑室内注射氯沙坦可抑制脑室内注射血管紧张素II引起的饮水；氯沙坦与AT2拮抗剂PD123319联合脑室内注射足以消除脑室内注射血管紧张素II引起的饮水。对于禁食24小时后进食和饮水的大鼠，皮下注射氯沙坦加PD123319可抑制水与食物的比例，但脑室内注射氯沙坦和/或PD123319未能抑制与食物相关的饮水。对于食用小饼干的未禁食大鼠，皮下注射氯沙坦和/或PD123319可减少水的摄入量，但只有脑室内注射氯沙坦对摄入饼干引起的饮水产生统计学上显著的抑制作用。通过手术植入的胃导管进行胃内输注2 ml 600或900 mOsm/kg NaCl，这种处理在饮水开始时对全身血浆渗透压升高的阈值以下，引起的饮水可被皮下注射氯沙坦和/或PD123319减弱，且仅被脑室内注射氯沙坦减弱。胃内输注2 ml 1800 mOsm/kg NaCl，这种处理在饮水开始时对全身血浆渗透压升高高于阈值，引起的饮水不受皮下或脑室内注射氯沙坦和/或PD123319的抑制。这些结果表明，血管紧张素II的外周AT1和AT2以及中枢AT1受体参与了进食引起的饮水以及进食的胃肠道渗透后果。这些发现扩展了证据，证明肾素-血管紧张素对大鼠与食物相关的饮水有贡献。
