CP-71,362: A Pentapeptide Renin Inhibitor Selective for the Canine Enzyme
| Autor: | Joseph T. MacAndrew, William F. Holt, S S Ellery, William R. Murphy, Irene M. Purcell, Kleinman Edward F, Andrew H. Smith, Michael L. Mangiapane |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
medicine.medical_specialty
Captopril Physiology medicine.drug_class Guinea Pigs Blood Pressure Pentapeptide repeat Plasma renin activity Renin inhibitor Guinea pig Dogs Rats Inbred SHR Internal medicine Renin Renin–angiotensin system Internal Medicine medicine Animals Humans chemistry.chemical_classification Dose-Response Relationship Drug biology Biological activity General Medicine Rats Macaca fascicularis Enzyme Endocrinology chemistry Enzyme inhibitor biology.protein Oligopeptides |
| Zdroj: | Clinical and Experimental Hypertension. 16:507-533 |
| ISSN: | 1525-6006 1064-1963 |
| Popis: | Most renin inhibitors are primate-specific. In the present paper, we describe the effects of CP-71,362, a pentapeptide which preferentially inhibits canine (and to a lesser extent, rat) plasma renin. Vs. the canine enzyme, its affinity (IC50 = 3.3 x 10(-12) M) is 1000x greater than for rat renin (IC50 = 3.3 x 10(-9) M), and 1000x greater than for human (IC50 = 2.3 x 10(-8) M), cynomolgus monkey (IC50 = 1.6 x 10(-8) M), or guinea pig (IC50 = 5.2 x 10(-8) M) enzyme. In anesthetized, sodium-depleted dogs, intravenous infusion of CP-71,362 (ED50 = 1.1 micrograms/kg/min) resulted in dose-dependent decreases (up to -35 mm Hg) in mean arterial pressure (MAP). The maximum fall in MAP was equivalent to that produced by i.v. captopril (5 mg/kg). Similar falls in MAP were observed in conscious sodium-depleted SHR (ED50 = 5 micrograms/kg/min). Via bolus injection, the action of CP-71,362 was relatively brief in dog, guinea pig, and SHR. We conclude that CP-71,362 is a potent canine/rat renin inhibitor and causes profound MAP lowering in these species. |
| Databáze: | OpenAIRE |
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