Antihypertensive Activity During Inhibition of Neutral Endopeptidase and Angiotensin Converting Enzyme
| Autor: | B.E. Abboa-Offei, Joel N. Swerdel, Andrea A. Seymour |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Male
medicine.medical_specialty Captopril Proline Angiotensin-Converting Enzyme Inhibitors Blood Pressure Pharmacology Organophosphorus Compounds Atrial natriuretic peptide Rats Inbred SHR Internal medicine Fosinopril medicine Animals Sulfhydryl Compounds cardiovascular diseases Amino Acids Neprilysin Antihypertensive Agents chemistry.chemical_classification biology Rats Inbred Strains Angiotensin-converting enzyme Endopeptidase Rats Endocrinology Enzyme chemistry Enzyme inhibitor Hypertension biology.protein Cardiology and Cardiovascular Medicine circulatory and respiratory physiology medicine.drug |
| Zdroj: | Journal of Cardiovascular Pharmacology. 17:456-465 |
| ISSN: | 0160-2446 |
| Popis: | The specific neutral endopeptidase (NEP) inhibitor, SQ 29,072 (7-[2-(mercaptomethyl)-1-oxo-3-phenylpropyl]amino]heptanoic acid), was studied in conscious spontaneously hypertensive rats (SHRs) and in DOCA/salt hypertensive rats during inhibition of angiotensin-converting enzyme (ACE) activity with captopril or SQ 27,519 (the free acid of fosinopril). In the SHR, the maximal depressor responses to the combination of SQ 29,072 and SQ 27,519 (-44 +/- 4 mm Hg) were greater than the responses to any of the inhibitors given alone (-26 +/- 5, -40 +/- 10, and -28 +/- 6 mm Hg for SQ 29,072, captopril, and SQ 27,519, respectively). In contrast, the maximal antihypertensive activities of SQ 29,072 were the same in conscious DOCA/salt hypertensive rats infused with saline, captopril, or SQ 27,519 (-54 +/- 10, -51 +/- 8, and -58 +/- 11 mm Hg, respectively), indicating a lack of synergism in this model. In agreement, SQ 28,133 [N-[2-(mercaptomethyl)-1-oxo-3-phenylpropyl]-L-leucine], a compound that inhibits both NEP and ACE, elicited significant depressor activities in both SHR and DOCA/salt hypertensive rats. In conclusion, a selective NEP inhibitor enhanced the depressor activity of ACE inhibitors in the conscious SHR, indicating that these agents may be effectively combined for treatment of some types of hypertension. |
| Databáze: | OpenAIRE |
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