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Comparative Antihypertensive Activities of Losartan and HM70186 in Rats with Hepatic Dysfunction
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  • Comparative Antihypertensive Activities of Losartan and HM70186 in Rats with Hepatic Dysfunction
  • Comparative Antihypertensive Activities of Losartan and HM70186 in Rats with Hepatic Dysfunction
저자명
Choi. Jae-Hong,Shin. Sun-Hee,Park. Dong-Sun,Jeon. Jeong-Hee,Choi. Bong-Ho,Jang. Min-Jung,Joo. Seong-Soo,Oh. Ki-Wan,Hong. Jin-Tae
간행물명
Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea
권/호정보
2009년|32권 7호|pp.1005-1011 (7 pages)
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대한약학회
파일정보
정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
서지반출

기타언어초록

HM70186, a medoxomil ester of EXP3174 which is an active metabolite of angiotensin II receptor blocker losartan, was synthesized, and its antihypertensive efficacy was evaluated in rats with hepatic dysfunction. Male Wistar rats were intraperitoneally injected with 0.5 mL/kg of carbon tetrachloride to cause hepatic injury, and implanted with an osmotic minipump containing angiotensin II (0.4 mg/kg/day) to induce hypertension. After confirmation of both hepatic damage and hypertension, the rats were orally administered losartan or HM70186, and then blood pressure and heart rate were monitored for 24 h. In normal animals, angiotensin II-induced hypertension was lowered by losartan, resulting in an $ED_{-30;mmHg}$ of 9.05 mg/kg. HM70186 also immediately decreased the blood pressure in a dose-dependent manner, exhibiting an $ED_{-30;mmHg}$ of 0.89 ng/kg (10,000 times the potency observed with losartan). Moreover, HM70186 (3 ng/kg) exerted a strong antihypertensive effect even in rats with hepatic injury, while losartan ($10;{mu}g/kg$) was ineffective. These results suggest that HM70186 could be a promising candidate for the treatment of hypertension accompanied by hepatic dysfunction.