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新型钙离子内流阻滞剂CD - 349和TMB - 8对犬血管紧张素II和血管升压素诱导的肾血管收缩的影响。

Effects of a novel Ca2+ entry blocker, CD-349, and TMB-8 on renal vasoconstriction induced by angiotensin II and vasopressin in dogs.

作者信息

Takahara A, Suzuki-Kusaba M, Hisa H, Satoh S

机构信息

Department of Pharmacology, Tohoku University, Sendai, Japan.

出版信息

J Cardiovasc Pharmacol. 1990 Dec;16(6):966-70. doi: 10.1097/00005344-199012000-00016.

DOI:10.1097/00005344-199012000-00016
PMID:1704991
Abstract

The effects of a Ca2+ entry blocker CD-349 and an intracellular Ca2+ release inhibitor TMB-8 on renal vasoconstriction induced by angiotensin II (ANG II) and arg-vasopressin (AVP) were examined in anesthetized dogs. Intrarenal bolus injection of ANG II (3-10 ng/kg), AVP (5-20 ng/kg) or a Ca2+ entry promotor Bay K 8644 (0.1-0.4 micrograms/kg) produced a dose-dependent decrease in renal blood flow (RBF). Intrarenal infusion of CD-349 (0.03-0.3 micrograms/kg/min) suppressed the RBF responses to ANG II, AVP, and Bay K 8644. The RBF responses to ANG II and AVP were augmented slightly by intrarenal infusion of Bay K 8644 (0.3 micrograms/kg/min). Intrarenal infusion of TMB-8 (0.03-0.1 mg/kg/min) also suppressed the RBF responses to ANG II and AVP, whereas it did not affect the RBF response to Bay K 8644. These results suggest that vasoconstriction induced by ANG II or AVP is mediated both by the influx of Ca2+ through dihydropyridine-sensitive Ca2+ channels and the release of Ca2+ from TMB-8-sensitive Ca2+ pools in the in vivo dog kidney.

摘要

在麻醉犬中研究了钙离子内流阻滞剂CD - 349和细胞内钙离子释放抑制剂TMB - 8对血管紧张素II(ANG II)和精氨酸加压素(AVP)诱导的肾血管收缩的影响。肾内推注ANG II(3 - 10 ng/kg)、AVP(5 - 20 ng/kg)或钙离子内流促进剂Bay K 8644(0.1 - 0.4微克/千克)可使肾血流量(RBF)呈剂量依赖性降低。肾内输注CD - 349(0.03 - 0.3微克/千克/分钟)可抑制对ANG II、AVP和Bay K 8644的RBF反应。肾内输注Bay K 8644(0.3微克/千克/分钟)可使对ANG II和AVP的RBF反应略有增强。肾内输注TMB - 8(0.03 - 0.1毫克/千克/分钟)也可抑制对ANG II和AVP的RBF反应,而对Bay K 8644的RBF反应无影响。这些结果表明,在体犬肾中,ANG II或AVP诱导的血管收缩是由通过二氢吡啶敏感性钙离子通道的钙离子内流和从TMB - 8敏感性钙离子池释放钙离子介导的。

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