Antihypertensive Effect of Calcium Entry Blockers

钙进入阻滞剂的抗高血压作用

• 批准号: 61570091
• 负责人: SATOH Susumu
• 金额: $ 1.28万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570091/
• 关键词: Calcium entry blocker; Nifedipine; Renal function; Vasoconstriction; Angiotensin II; 交換神経α受容体; ニフエジピン; 腎血管収縮; バソプレシン; アンジオテンシン【II】; 利尿作用

The present study was performed to clarify the antihypertensive effects of calcium entry blockers using anesthetized dogs and pithed rats.1. Intrarenal infusion of nifedipine and CD-349, calcium entry blockers, produced marked increase in urine flow rate and in urinary sodium and potassium excretion rates of the infused kidney without changes in heart rate, glomerular filtration rate and filtration fraction. Urinary osmolarity was decreased by the drugs. The blood flow to the infused kidney was increased. These results suggest that nifedipine and CD-349 have striking effects on the reabsorption of sodium and water by the renal tubule (Reference 1).2. Intrarenal infusion of nifedipine and CD-349 dose-dependently suppressed the renal vasoconstriction induced by intrarenal injections of angiotensin II (AII) or norepinephrine but not that by renal nerve stimulation. Furthermore, a greater renal vasodilation induced by intrarenal bolus injections of nifedipine but not acetylcholine was obse … More rved during the reduction of the perfusion pressure of the contralateral kidney, which resulted in an increase in plasma renin activity and plasma AII concentration (Reference 2).3. In pithed rats, nifedipine inhibited the vasoconstrictor responses to alpha-2-adrenoceptor agonist B-HT 920, and AII but not to the alpha-1-adrenoceptor agonist methoxamine, and vasopressin. CD-349 reduced the pressor responses to all the above agonists. After pretreatment of calcium channel promotor Bay K 8644, the inhibition of CD-349 observed for AII, B-HT 920 and vasopressin was antagonized. These results suggest that AII-, alpha-2-adrenoceptor-mediated vasoconstrictions are sensitive to calcium entry blockade with calcium antagonists, but the vasoconstriction induced by the alpha-1-adrenoceptor-mediated agonist is not primarily dependent upon an influx of calcium. And it is possible that transcellular calcium influx may be common pathway in the vasoconstriction elicited by alpha-2-agonist B-HT 920 and AII. Less

本研究采用麻醉犬和去髓大鼠，研究钙通道阻滞剂的降压作用。肾内输注硝苯地平和CD-349（钙离子进入阻滞剂）可显著增加输注肾脏的尿流率和尿钠和尿钾排泄率，而心率、肾小球滤过率和滤过分数无变化。药物可降低尿渗透压。输注肾脏的血流量增加。这些结果表明硝苯地平和CD-349对肾小管对钠和水的重吸收具有显著影响（参考文献1）。硝苯地平和CD-349的肾内输注剂量依赖性地抑制肾内注射血管紧张素II（AII）或去甲肾上腺素引起的肾血管收缩，但不是由肾神经刺激。此外，肾内推注硝苯地平而非乙酰胆碱可引起更大的肾血管舒张， ...更多信息 在对侧肾脏灌注压降低期间，这导致血浆肾素活性和血浆AII浓度增加（参考文献2）。硝苯地平抑制α 2肾上腺素受体激动剂B-HT 920和AII的血管收缩反应，但不抑制α 1肾上腺素受体激动剂甲氧胺和加压素。CD-349可降低对上述所有激动剂的升压反应。经钙通道促进剂Bay K 8644预处理后，CD-349对AII、B-HT 920和加压素的抑制作用被拮抗。这些结果表明，AII-，α-2-肾上腺素受体介导的血管收缩是敏感的钙离子通道阻滞剂与钙拮抗剂，但α-1-肾上腺素受体介导的激动剂诱导的血管收缩是不是主要依赖于钙离子的流入。跨细胞钙内流可能是α 2受体激动剂B-HT 920和AII引起血管收缩的共同途径。少

项目成果

Jun-ichi Imagawa, Hideo Kurosawa and Susumu Satoh: "Effects of Nifedipine on Renin Release and Renal Function in Anesthetized Dogs." Journal of Cardiovascular Pharmacology. 8. 636-640 (1986)

Jun-ichi Imakawa、Hideo Kurosawa 和 Susumu Satoh：“硝苯地平对麻醉犬肾素释放和肾功能的影响”。

Jun-ichi Imagawa, Mizue Suzuki-Kusaba and Susumu Satoh: "Preferential Inhibitory Effect of Nifedipine on Angiotensin II-Induced Renal Vasoconstriction" Hypertension. 8. 893-903 (1986)

Jun-ichi Imakawa、Mizue Suzuki-Kusaba 和 Susumu Satoh：“硝苯地平对血管紧张素 II 诱导的肾血管收缩的优先抑制作用”高血压。

今川純一: Journal of Cardiovascular Pharmacology. 8. 636-640 (1986)

今川纯一：心血管药理学杂志。8. 636-640 (1986)

今川純一: Hypertension. 8. 893-903 (1986)

今川纯一：高血压。8. 893-903 (1986)