Department of Pathophysiology, Medical University of Gdansk, Gdansk, Poland.
J Physiol Pharmacol. 2010 Apr;61(2):163-70.
Calcilytics, antagonists of calcium receptor, decrease sensitivity of this receptor to plasma calcium concentration and increase parathyroid hormone (PTH) secretion. Moreover, it was recently indicated that calcilytic NPS 2143 induces hypertension in rats. This study tested whether the increase of mean arterial blood pressure (MAP) induced by NPS 2143 administration is mediated by calcium channel and angiotensin II type 1 (AT1) receptor activity. Wistar rats were anaesthesized with Thiopental i.p. and infused i.v. with saline supplemented with the anaesthetic. Blood pressure was monitored continuously in the carotid artery. Effects of NPS 2143 administered i.v. as bolus on MAP in the presence and absence of felodypine and losartan were investigated. Both, felodipine and losartan pretreatment provoked a persistent DMAP decrease by 18+/-3 and 14+/-3 mmHg, respectively. Infusion of NPS 2143 at 1 mg/kg b.w. confirmed hypertensive activity of calcilytic and increased blood pressure for 21+/-4 mmHg. In contrast, administration of NPS 2143 in felodipine as well as in losartan pretreated rats did not change DMAP as compared to felodipine/control and losartan/control groups, respectively. Our study indicated that both the blockade of calcium channels and the AT1 receptor activity prevented the hypertensive effect of calcilytic NPS 2143. This finding might be particularly important in understanding the mechanisms that mediated blood pressure changes related to the activity of calcium receptor.
钙敏感受体拮抗剂降低了钙敏感受体对血浆钙离子浓度的敏感性，并增加甲状旁腺激素（PTH）的分泌。此外，最近有研究表明钙敏感受体拮抗剂 NPS 2143 可引起大鼠高血压。本研究旨在探讨 NPS 2143 引起的平均动脉血压（MAP）升高是否与钙通道和血管紧张素 II 型 1（AT1）受体活性有关。采用腹腔注射硫喷妥钠麻醉 Wistar 大鼠，通过静脉输注生理盐水补充麻醉剂。通过颈动脉连续监测血压。研究了静脉注射 NPS 2143 对 MAP 的影响，同时观察了 felodipine 和 losartan 的存在和缺失对其的影响。Felodipine 和 losartan 预处理分别使 DMAP 持续降低 18+/-3 和 14+/-3mmHg。静脉注射 NPS 2143 （1mg/kg b.w.）证实了钙敏感受体激动剂的升压活性，并使血压升高 21+/-4mmHg。相比之下，在 felodipine 和 losartan 预处理的大鼠中给予 NPS 2143 并未改变 DMAP，与 felodipine/对照和 losartan/对照组相比分别无差异。本研究表明，钙通道阻断和 AT1 受体活性的阻断均可预防钙敏感受体激动剂 NPS 2143 的升压作用。这一发现对于理解与钙受体活性相关的血压变化机制可能尤为重要。
