Rossi Noreen F, Chen Haiping
Departments of Medicine and Physiology, Wayne State University School of Medicine and John D. Dingell VA Medical Center, 4160 John R Street, #908, Detroit, Michigan 48201, USA.
Exp Biol Med (Maywood). 2006 Jun;231(6):1075-80.
Endothelin-1 (ET-1) acts at selected brain loci to elicit a pressor response and secretion of vasopressin (AVP). Glutamatergic receptors of the N-methyl-D-aspartate (NMDA) subtype mediate ET-1-induced AVP secretion in vitro, but the role of glutamatergic receptors in the pressor response and the secretion of AVP in vivo has not been studied. We hypothesized that both the pressor response and AVP secretion in response to ET-1 microinjection into subfornical organ (SFO) would be suppressed by ionotropic glutamatergic receptor antagonists in the paraventricular nucleus (PVN). Sinoaortic denervated male Long Evans rats were equipped with intracerebral cannulae directed into the SFO and the magnocellular region of the PVN bilaterally. Experiments were performed 5 days later in conscious rats. Direct injection of 5 pmol ET-1 into the SFO resulted in a 20 +/- 3 mm Hg increase in mean arterial pressure (MAP) (+/- SE) and a 14.1 +/- 0.3 pg/ml increase in the mean plasma AVP level (+/- SE) (P < 0.001 vs. artificial CSF) that was blocked by selective ET(A) inhibition. Neither the pressor response nor the increase in plasma AVP in response to ET-1 was altered despite prior injection of the NMDA blocker diclozipine (5 microg, MK801) into PVN bilaterally. In contrast, bilateral PVN injection with 6-cyano-7-nitroquinoxaline-2,3-dione (40 nmol, CNQX) prevented the pressor response (MAP +/- SE, - 4 +/- 4 mm Hg) and also inhibited AVP secretion (mean AVP level +/- SE, 0.16 +/- 0.50 pg/ml) (P < 0.001 vs. vehicle in PVN after injection of ET-1 into SFO). These findings support the conclusion that both the pressor response and AVP secretion in response to ET-1 acting at the SFO are mediated by a non-NMDA, most likely an aminopropionic acid glutamatergic receptor within the PVN.
内皮素 -1（ET-1）作用于特定脑区，引发升压反应并促使血管加压素（AVP）分泌。N-甲基-D-天冬氨酸（NMDA）亚型的谷氨酸能受体在体外介导ET-1诱导的AVP分泌，但谷氨酸能受体在体内升压反应及AVP分泌中的作用尚未得到研究。我们推测，向室旁核（PVN）注射离子型谷氨酸能受体拮抗剂会抑制向穹窿下器（SFO）微量注射ET-1所引发的升压反应和AVP分泌。对雄性长爪沙鼠进行去窦弓神经处理，并双侧植入分别指向SFO和PVN大细胞区的脑内套管。5天后在清醒大鼠身上进行实验。向SFO直接注射5皮摩尔ET-1可使平均动脉压（MAP）升高20±3毫米汞柱（±标准误），平均血浆AVP水平升高14.1±0.3皮克/毫升（±标准误）（与人工脑脊液相比，P<0.001），这一效应可被选择性ET(A)抑制所阻断。尽管事先双侧PVN注射了NMDA阻滞剂二氯西平（5微克，MK801），但ET-1引发的升压反应和血浆AVP升高均未改变。相反，双侧PVN注射6-氰基-7-硝基喹喔啉-2,3-二酮（40纳摩尔，CNQX）可阻止升压反应（MAP±标准误，-4±4毫米汞柱），并抑制AVP分泌（平均AVP水平±标准误，0.16±0.50皮克/毫升）（与向SFO注射ET-1后PVN注射溶媒相比，P<0.001）。这些发现支持以下结论：作用于SFO的ET-1所引发的升压反应和AVP分泌均由非NMDA受体介导，很可能是PVN内的丙氨酸型谷氨酸能受体。
