Qadri F, Waldmann T, Wolf A, Höhle S, Rascher W, Unger T
Institute of Pharmacology, University of Kiel, Kiel, Germany.
J Pharmacol Exp Ther. 1998 Jun;285(3):1012-8.
We studied the involvement of periventricular and hypothalamic angiotensinergic and cholinergic pathways in osmotically induced arginine vasopressin (AVP) release into the blood. In conscious Wistar rats, i.c.v. injections of 0.2, 0.3 and 0.6 M hyperosmolar saline (5 microl) resulted in concentration-dependent increases in AVP release (5.2 +/- 1.5, 10.6 +/- 2.2 and 18.0 +/- 2.2 pg/ml, respectively, vs. 2.0 +/- 0.1 in controls). The two lower saline concentrations did not affect arterial blood pressure (non-pressure-associated AVP release), whereas 0.6 M saline induced increase in blood pressure (pressure-associated AVP release). In the first set of experiments, periventricular angiotensin AT1, muscarinic or nicotinic receptors were blocked by i.c.v. administration of losartan (10 nmol), atropine (100 nmol) or hexamethonium (100 nmol), respectively, before i.c.v. hyperosmolar saline injections. Losartan significantly reduced the 0.2 M and 0.3 M, but not the 0.6 M, saline-induced increase in AVP release. The 0. 3 M saline-induced AVP release was blocked by atropine and hexamethonium, whereas the 0.6 M saline-induced AVP release was blocked by atropine only. In the second set of experiments, losartan (4 nmol), atropine (200 nmol) or hexamethonium (200 nmol) was injected bilaterally into the paraventricular nucleus before i.c.v. hyperosmolar saline injections. Losartan reduced 0.3 M and potentiated 0.6 M saline-induced AVP release. On the other hand, atropine and hexamethonium significantly reduced both 0.3 and 0.6 M saline-induced AVP release. We conclude that afferents arising from periventricular osmosensitive neurons to the hypothalamic paraventricular nucleus, which are involved in non-pressure-associated osmotically induced AVP release, are both angiotensinergic and cholinergic, whereas those mediating pressure-associated AVP release are cholinergic in nature.
我们研究了室周和下丘脑的血管紧张素能及胆碱能通路在渗透压诱导的精氨酸加压素(AVP)释放进入血液过程中的作用。在清醒的Wistar大鼠中,脑室内注射0.2、0.3和0.6 M的高渗盐水(5微升)导致AVP释放呈浓度依赖性增加(分别为5.2±1.5、10.6±2.2和18.0±2.2皮克/毫升,而对照组为2.0±0.1)。较低的两种盐水浓度不影响动脉血压(与压力无关的AVP释放),而0.6 M盐水可引起血压升高(与压力相关的AVP释放)。在第一组实验中,在脑室内注射高渗盐水之前,分别通过脑室内给药氯沙坦(10纳摩尔)、阿托品(100纳摩尔)或六甲铵(100纳摩尔)来阻断室周血管紧张素AT1、毒蕈碱或烟碱受体。氯沙坦显著降低了0.2 M和0.3 M盐水诱导的AVP释放增加,但未降低0.6 M盐水诱导的增加。0.3 M盐水诱导的AVP释放被阿托品和六甲铵阻断,而0.6 M盐水诱导的AVP释放仅被阿托品阻断。在第二组实验中,在脑室内注射高渗盐水之前,将氯沙坦(4纳摩尔)、阿托品(200纳摩尔)或六甲铵(200纳摩尔)双侧注射到室旁核。氯沙坦降低了0.3 M盐水诱导的AVP释放,并增强了0.6 M盐水诱导的释放。另一方面,阿托品和六甲铵显著降低了0.3 M和0.6 M盐水诱导的AVP释放。我们得出结论,起源于室周渗透压敏感神经元至下丘脑室旁核的传入神经,参与与压力无关的渗透压诱导的AVP释放,既具有血管紧张素能又具有胆碱能,而介导与压力相关的AVP释放的传入神经本质上是胆碱能的。