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.
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Authors | H Saitoh, Y Etoh, M Murakami, T Kubota, M Miyazaki |
Journal | Nihon yakurigaku zasshi. Folia pharmacologica Japonica
(Nihon Yakurigaku Zasshi)
Vol. 103
Issue 4
Pg. 161-73
(Apr 1994)
ISSN: 0015-5691 [Print] Japan |
PMID | 8175079
(Publication Type: English Abstract, Journal Article)
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Chemical References |
- Antihypertensive Agents
- Dipeptides
- Morpholines
- Naphthalenes
- KRI 1314
- Renin
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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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