自然発症高血圧ラット（ＳＨＲ）の高血圧発症に対する（２Ｒ，４Ｒ）‐２‐（ｏ‐Ｈｙｄｒｏｘｙｐｈｅｎｙｌ）‐３‐（３‐ｍｅｒｃａｐｔｏｐｒｏｐｉｏｎｙｌ）‐４‐ｔｈｉａｚｏｌｉｄｉｎｅｃａｒｂｏｘｙｌｉｃ　ａｃｉｄとＨｙｄｒｏｃｈｌｏｒｏｔｈｉａｚｉｄｅあるいはＰｒｏｐｒａｎｏｌｏｌとの長期併用効果

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  • Combined effect of (2R, 4R)-2-(o-hydroxyphenyl)-3-(3-mercaptopropionyl)-4-thiazolidinecarboxylic acid (SA446) with hydrochlorothiazide or propranolol on development of hypertension in spontaneously hypertensive rats (SHR) by long-term administration.
  • シゼン ハツショウ コウケツアツ ラット SHR ノ コウケツアツ ハツショウ

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Effect of long-term oral administration of the converting enzyme inhibitor (2R, 4R)-2-(o-hydroxyphenyl)-3-(mercaptopropionyl)-4-thiazolidinecarboxylic acid (SA446) in combination with hydrochlorothiazide or propranolol on the development of hypertension was examined in spontaneously hypertensive rats (SHR). The development of hypertension in SHR was markedly suppressed by the treatment with SA446 (45 mg/kg, p.o.) for 17 weeks from 8 weeks of age, the pre-stage of hypertension. Long-term administration of hydrochlorothiazide (20 mg/kg, p.o.) also showed an obvious antihypertensive effect, but the effect was less potent than that of SA446. On the other hand, propranolol (20 mg/kg, p.o.) showed a slight or little antihypertensive effect. The combined administration of hydrochlorothiazide and SA446 produced a more potent antihypertensive effect than the administration of SA446 alone. On the other hand, the combined use of propranolol had no influence on the antihypertensive effect of SA446 by long-term administration in SHR. Plasma renin activities measured after 17 weeks treatment of the drugs indicated that the reninangiotensin system was activated by hydrochlorothiazide. These results suggest that the antihypertensive effect of long-term administration of SA446 in SHR is enhanced by the combined administration of diuretics such as hydrochlorothiazide, which activates the renin-angiotensin system.

収録刊行物

  • 日本薬理学雑誌

    日本薬理学雑誌 87 (3), 331-337, 1986

    公益社団法人 日本薬理学会

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