Abstract | BACKGROUND: METHODS AND RESULTS: After a 4-week placebo run-in period, 124 patients with a mean blood pressure of 162/102 mm Hg were randomized in a double-blind parallel-group design to 1 of 5 treatments, given once daily for 10 days: 50 mg, 100 mg, or 200 mg sampatrilat; 20 mg lisinopril; or placebo. The first dose of sampatrilat did not lower clinic or ambulatory blood pressure. Lisinopril had an immediate antihypertensive effect that differed significantly from all doses of sampatrilat. After 10 days of treatment, sampatrilat lowered clinic and ambulatory blood pressure significantly at all doses, with a trend toward a dose response for systolic ambulatory blood pressure. Sampatrilat inhibited plasma ACE in a dose-dependent fashion but significantly less so than lisinopril on days 1 and 10 of treatment. Lisinopril but not sampatrilat significantly increased plasma renin activity, whereas sampatrilat but not lisinopril significantly increased urinary cGMP excretion. CONCLUSION: The increasing efficacy of sampatrilat compared with lisinopril over 10 days could not be attributed to an increase in plasma ACE inhibition, suggesting that the NEP inhibitor activity of sampatrilat may have contributed to its antihypertensive action. NEP inhibition may enhance the antihypertensive effect of ACE inhibition.
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Authors | E J Wallis, L E Ramsay, J Hettiarachchi |
Journal | Clinical pharmacology and therapeutics
(Clin Pharmacol Ther)
Vol. 64
Issue 4
Pg. 439-49
(Oct 1998)
ISSN: 0009-9236 [Print] United States |
PMID | 9797801
(Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiotensin-Converting Enzyme Inhibitors
- Antihypertensive Agents
- Mesylates
- Tyrosine
- Guanosine Monophosphate
- Lisinopril
- Renin
- Neprilysin
- sampatrilat
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Topics |
- Adult
- Aged
- Angiotensin-Converting Enzyme Inhibitors
(pharmacology, therapeutic use)
- Antihypertensive Agents
(pharmacology, therapeutic use)
- Blood Pressure
(drug effects)
- Dose-Response Relationship, Drug
- Double-Blind Method
- Female
- Guanosine Monophosphate
(urine)
- Humans
- Hypertension
(drug therapy, enzymology)
- Lisinopril
(pharmacology)
- Male
- Mesylates
(pharmacology, therapeutic use)
- Middle Aged
- Neprilysin
(antagonists & inhibitors)
- Renin
(blood)
- Tyrosine
(analogs & derivatives, pharmacology, therapeutic use)
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