Ichihara A, Suzuki H, Murakami M, Naitoh M, Matsumoto A, Saruta T
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Eur J Endocrinol. 1995 Nov;133(5):569-77. doi: 10.1530/eje.0.1330569.
While the interactions between angiotensin II (Ang II) and norepinephrine (NE) on cardiovascular responses are well known, their effects on renin responses are not. We determined the renin secretion rate (RSR) and intracellular calcium level in juxtaglomerular cells harvested from Sprague-Dawley rats using a radioimmunoassay and a two-dimensional calcium analyzer. The effect of Ang II and NE was inhibitory on RSR and stimulatory on intracellular calcium. The NE-induced RSR response was amplified in the presence of Ang II (20 nmol/l). The NE-induced intracellular calcium response was also potentiated by the Ang II. There was a significant correlation (r = 0.994, p < 0.0001) between the changes in the RSR and those in intracellular calcium levels. Losartan (0.1 mumol/l). an Ang II type 1 receptor antagonist, blocked the Ang II threshold RSR responses and completely abolished the Ang II-related enhancements. The exclusion of calcium from the buffer reduced the maximal RSR response to NE but did not prevent the enhancement, suggesting the importance of the mobilization of intracellular calcium in the mechanism. The Ang II-induced RSR was amplified in the presence of NE (0.2 mumol/l). The Ang II-induced intracellular calcium response was also potentiated by the NE. A significant correlation (r = 0.996, p < 0.0001) between the changes in the RSR and the changes in intracellular calcium levels was also noted. Prazosin (1 mumol/l), an alpha 1-adrenoceptor antagonist, blocked the NE threshold RSR responses and abolished the agonist-related enhancements. The calcium-free buffer diminished this amplication with a slight decrease in the maximum RSR response to Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)
虽然血管紧张素II(Ang II)与去甲肾上腺素(NE)对心血管反应的相互作用已为人熟知,但其对肾素反应的影响却并非如此。我们使用放射免疫分析法和二维钙分析仪,测定了从Sprague-Dawley大鼠采集的球旁细胞中的肾素分泌率(RSR)和细胞内钙水平。Ang II和NE对RSR具有抑制作用,对细胞内钙具有刺激作用。在存在Ang II(20 nmol/l)的情况下,NE诱导的RSR反应增强。Ang II也增强了NE诱导的细胞内钙反应。RSR的变化与细胞内钙水平的变化之间存在显著相关性(r = 0.994,p < 0.0001)。氯沙坦(0.1 μmol/l),一种Ang II 1型受体拮抗剂,阻断了Ang II阈值RSR反应,并完全消除了与Ang II相关的增强作用。从缓冲液中去除钙降低了对NE的最大RSR反应,但并未阻止增强作用,表明细胞内钙动员在该机制中的重要性。在存在NE(0.2 μmol/l)的情况下,Ang II诱导的RSR增强。Ang II诱导的细胞内钙反应也被NE增强。RSR的变化与细胞内钙水平的变化之间也存在显著相关性(r = 0.996,p < 0.0001)。哌唑嗪(1 μmol/l),一种α1肾上腺素能受体拮抗剂,阻断了NE阈值RSR反应,并消除了激动剂相关的增强作用。无钙缓冲液减少了这种增强作用,同时对Ang II的最大RSR反应略有降低。(摘要截断于250字)