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Comparative antihypertensive activities of losartan and HM70186 in rats with hepatic dysfunction

Archives of Pharmacal Research volume 32, pages 1005–1011 (2009)Cite this article

Abstract

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 μg/kg) was ineffective. These results suggest that HM70186 could be a promising candidate for the treatment of hypertension accompanied by hepatic dysfunction.

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Authors and Affiliations

  1. College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju, 361-763, Korea

    Jae-Hong Choi, Sunhee Shin, Dongsun Park, Jeong Hee Jeon, Bong Ho Choi, Min-Jung Jang, Seong Soo Joo & Yun-Bae Kim

  2. College of Pharmacy, Chungbuk National University, Cheongju, 361-763, Korea

    Ki-Wan Oh & Jin Tae Hong

  3. Research Center, Hanmi Pharmaceutical Co., Ltd., Hwaseong, 445-813, Korea

    Kwee-Hyun Suh

  4. College of Veterinary Medicine, Chungbuk National University, Cheongju, 361-763, Korea

    Yun-Bae Kim

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  1. Jae-Hong Choi
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  2. Sunhee Shin
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  3. Dongsun Park
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Correspondence to Yun-Bae Kim.

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Choi, JH., Shin, S., Park, D. et al. Comparative antihypertensive activities of losartan and HM70186 in rats with hepatic dysfunction. Arch. Pharm. Res. 32, 1005–1011 (2009). https://doi.org/10.1007/s12272-009-1705-0

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  • DOI: https://doi.org/10.1007/s12272-009-1705-0

Key words

  • Hypertension
  • Angiotensin II
  • Losartan
  • HM70186
  • Hepatic dysfunction