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[Hypotensive action of human renin inhibitor KRI-1314 in the common marmoset].

Abstract
The possibility of using KRI-1314, a new cyclohexylnorstatine derivative, as an antihypertensive drug was examined using common marmosets. KRI-1314 strongly inhibited plasma renin activity (PRA) in both humans and marmosets, with a 50% inhibitory concentration of 4.7 x 10(-9) and 6.9 x 10(-9) M, respectively. In anesthetized marmosets, the increase in both blood pressure and PRA induced by bolus intravenous injection of RH-renin (0.15 microgram/kg) was suppressed by constant intravenous infusion of KRI-1314 (0.01 and 0.1 mg/kg/min) in a dose-dependent manner. In the sustained hypertension induced by continuous intravenous infusion of RH-renin (0.1 microgram/kg/min), a dose-dependent hypotensive response was produced by bolus intravenous injection of KRI-1314 (0.03-3 mg/kg). In the sodium-depleted model, whose PRA was increased by a two-week low-sodium diet coupled with furosemide loading, both intravenous injection (0.1-3 mg/kg) and oral administration (10 and 30 mg/kg) of KRI-1314 to anesthetized and conscious animals, respectively, lowered blood pressure dose-dependently with PRA suppression. The hypotensive activity of orally administered KRI-1314 (30 mg/kg) was almost equal to that of orally administered captopril (1 mg/kg). KRI-1314 did not affect heart rate in any of the experiments. These results indicate that the potent human renin inhibitor KRI-1314 may become an orally effective drug for treating renin-dependent hypertension.
AuthorsH Saitoh, Y Etoh, M Murakami, T Kubota, M Miyazaki
JournalNihon yakurigaku zasshi. Folia pharmacologica Japonica (Nihon Yakurigaku Zasshi) Vol. 103 Issue 4 Pg. 161-73 (Apr 1994) ISSN: 0015-5691 [Print] Japan
PMID8175079 (Publication Type: English Abstract, Journal Article)
Chemical References
  • Antihypertensive Agents
  • Dipeptides
  • Morpholines
  • Naphthalenes
  • KRI 1314
  • Renin
Topics
  • Administration, Oral
  • Animals
  • Antihypertensive Agents (pharmacology)
  • Blood Pressure (drug effects)
  • Callithrix
  • Diet, Sodium-Restricted
  • Dipeptides (administration & dosage, pharmacology)
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Morpholines (administration & dosage, pharmacology)
  • Naphthalenes (administration & dosage, pharmacology)
  • Renin (antagonists & inhibitors)

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