Grillo C A, Saravia F, Ferrini M, Piroli G, Roig P, García S I, de Kloet E R, De Nicola A F
Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, University of Buenos Aires, Argentina.
Neuroendocrinology. 1998 Aug;68(2):105-15. doi: 10.1159/000054356.
The neuropeptides arginine vasopressin (AVP) and oxytocin (OT) have been implicated in the genesis of hypertension due to deoxycorticosterone acetate (DOCA)-salt treatment of uninephrectomized rats. In this work, we studied if DOCA treatment of intact rats in doses arousing a salt appetite (a prehypertensive state), modulated mRNA for AVP and OT in the hypothalamus. Male Sprague-Dawley rats were offered both tap water and 3% NaCl in separate bottles and received vehicle or subcutaneous injections of 10 mg DOCA on alternate days for 7 days (4 injections) or 17 days (9 injections). They developed a preference for 3% NaCl solutions 24-48 h after treatment. Brain slices from rats killed on the 8th or 18th day were exposed to 35S-labeled probes encoding prepro-AVP mRNA or OT mRNA, respectively. Expression of these mRNAs was measured in the magnocellular and parvocellular divisions of the paraventricular nucleus (PVN) and magnocellular cells of the supraoptic nucleus (SON). No changes were obtained in neuropeptide mRNA levels in the parvocellular division of the PVN between control and the two groups of DOCA-treated rats. However, DOCA-treated animals presented an increased number of grains per cell for AVP mRNA in the magnocellular division of the PVN and in magnocellular cells of the SON, as shown by group mean comparisons and frequency histograms. No changes were detected for OT mRNA. In a second series of studies, control or DOCA-treated rats were offered 3% NaCl or water as the only choice. Animals drinking 3% NaCl showed increased AVP and OT mRNA levels, whether they received DOCA or not. However, AVP mRNA levels in both nuclei were higher in DOCA-treated rats drinking 3% NaCl than in controls drinking salt solution. In comparison, control and DOCA-treated rats drinking water showed lower levels of AVP mRNA. OT mRNA levels in the SON remained unchanged in the same groups. The results suggest that in the magnocellular cells of the PVN and SON, increments in AVP mRNA are obtained following increments in salt intake produced by either mineralocorticoid treatment or exclusive salt drinking. In rats offered salt solution and water to drink, DOCA effects on AVP mRNA developed before changes occurred in serum sodium levels. Because combined DOCA + salt treatment induced a higher response in terms of AVP mRNA expression, we suggest that AVP could be a target of the central effects of the mineralocorticoid.
神经肽精氨酸加压素（AVP）和催产素（OT）与去氧皮质酮醋酸盐（DOCA）-盐处理单侧肾切除大鼠所致高血压的发生有关。在本研究中，我们探究了用能引起盐食欲（一种高血压前期状态）的剂量对完整大鼠进行DOCA处理，是否会调节下丘脑AVP和OT的mRNA水平。雄性Sprague-Dawley大鼠分别提供自来水和3% NaCl溶液，每隔一天接受载体或皮下注射10 mg DOCA，共7天（4次注射）或17天（9次注射）。处理后24 - 48小时，它们对3% NaCl溶液产生了偏好。分别在第8天或第18天处死大鼠，取脑片，用编码前体AVP mRNA或OT mRNA的35S标记探针进行杂交。在室旁核（PVN）的大细胞和小细胞部以及视上核（SON）的大细胞中测量这些mRNA的表达。对照组与两组DOCA处理大鼠的PVN小细胞部神经肽mRNA水平无变化。然而，通过组均值比较和频率直方图显示，DOCA处理的动物PVN大细胞部和SON大细胞中AVP mRNA的每个细胞颗粒数增加。OT mRNA未检测到变化。在第二项系列研究中，对照组或DOCA处理的大鼠只能选择3% NaCl或水。饮用3% NaCl的动物，无论是否接受DOCA处理，AVP和OT mRNA水平均升高。然而，饮用3% NaCl的DOCA处理大鼠两个核中的AVP mRNA水平高于饮用盐溶液的对照组。相比之下，饮用自来水的对照组和DOCA处理大鼠的AVP mRNA水平较低。同一组中SON的OT mRNA水平保持不变。结果表明，在PVN和SON的大细胞中，盐皮质激素处理或单纯饮用盐溶液导致盐摄入量增加后，AVP mRNA水平升高。在提供盐溶液和水饮用的大鼠中，DOCA对AVP mRNA的影响在血清钠水平变化之前就已出现。由于联合DOCA +盐处理在AVP mRNA表达方面诱导了更高的反应，我们认为AVP可能是盐皮质激素中枢作用的靶点。
