Kovács K J, Antoni F A
Department of Human Anatomy, University of Oxford, England.
Endocrinology. 1990 Dec;127(6):3003-8. doi: 10.1210/endo-127-6-3003.
The aim of this study was to resolve previous controversies regarding the effect of atriopeptin on the secretion of ACTH in vivo. Male Wistar rats were used throughout. The animals were subjected to lesioning of the hypothalamic paraventricular nucleus (PVN) or sham operation and implanted with indwelling jugular cannulae 5 days later for blood sampling and drug infusion. Two days after the insertion of the cannulae the animals were treated with saline or 103-126 amino acid residue atriopeptin iv: a bolus injection was given (200 or 40 pmol/rat) followed by an infusion (40 or 8 pmol/min) which was maintained for the entire duration of the experiment (70 min). Ten minutes after the bolus of atriopeptin the animals received iv a combination of 1 pmol 41-residue CRF and 10 pmol arginine vasopressin (CRF/AVP) to stimulate ACTH secretion. Serial blood samples (0.1 ml) were obtained at -10 min and immediately before the injection of CRF/AVP and at 5, 10, 20, 30, and 60 min afterwards. Plasma ACTH concentration was measured by RIA. In sham-operated rats CRF/AVP caused a 4-fold increase in plasma ACTH which peaked at 5 min and returned to baseline by 60 min. In sham-operated rats the higher dose of atriopeptin (200 pmol bolus, 40 pmol/min infusion) did not alter the effect of the stimulus between 5 and 30 min, and augmented plasma ACTH at 60 min. The smaller dose of atriopeptin reduced plasma ACTH at 10 and 20 min by 54% and 48%, respectively, and also decreased by 48% the net amount of ACTH released over 30 min in response to CRF/AVP. When given alone, the higher dose of atriopeptin caused a persistent (60 min) 10-13% reduction of mean arterial blood pressure, while the lower dose decreased blood pressure by about 9% for less than 10 min. In parallel, the higher dose of atriopeptin increased plasma ACTH concentration while the lower dose produced no change. In PVN-lesioned rats the CRF/AVP induced ACTH response was similar to that seen in sham-operated controls. Only the higher dose of atriopeptin was tested, and this markedly reduced CRF/AVP stimulated ACTH secretion at 5-60 min after CRF/AVP. Given alone, atriopeptin had no marked effect on plasma ACTH in PVN-lesioned rats, while its hypotensive action was similar to that in sham-operated animals.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究的目的是解决先前关于心房肽对体内促肾上腺皮质激素（ACTH）分泌影响的争议。实验全程使用雄性Wistar大鼠。对动物进行下丘脑室旁核（PVN）损伤或假手术，并在5天后植入颈静脉留置套管用于采血和药物输注。插入套管两天后，给动物静脉注射生理盐水或103 - 126个氨基酸残基的心房肽：先给予一次推注（200或40 pmol/大鼠），随后进行输注（40或8 pmol/分钟），持续整个实验过程（70分钟）。在推注心房肽10分钟后，给动物静脉注射1 pmol 41个残基的促肾上腺皮质激素释放因子（CRF）和10 pmol精氨酸加压素（CRF/AVP）的组合以刺激ACTH分泌。在 - 10分钟、注射CRF/AVP前即刻以及注射后5、10、20、30和60分钟采集系列血样（0.1 ml）。用放射免疫分析法（RIA）测定血浆ACTH浓度。在假手术大鼠中，CRF/AVP使血浆ACTH增加4倍，在5分钟时达到峰值，并在60分钟时恢复到基线水平。在假手术大鼠中，较高剂量的心房肽（200 pmol推注，40 pmol/分钟输注）在5至30分钟内未改变刺激效果，但在60分钟时增加了血浆ACTH。较小剂量的心房肽分别在10和20分钟时使血浆ACTH降低54%和48%，并且在30分钟内对CRF/AVP反应释放的ACTH总量也减少了48%。单独给予时，较高剂量的心房肽使平均动脉血压持续（60分钟）降低10 - 13%，而较低剂量在不到10分钟内使血压降低约9%。同时，较高剂量的心房肽增加了血浆ACTH浓度，而较低剂量则无变化。在PVN损伤的大鼠中，CRF/AVP诱导的ACTH反应与假手术对照组相似。仅测试了较高剂量的心房肽，其在CRF/AVP后5 - 60分钟显著降低了CRF/AVP刺激的ACTH分泌。单独给予时，心房肽对PVN损伤大鼠的血浆ACTH无明显影响，但其降压作用与假手术动物相似。（摘要截短至400字）
