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Combined inhibition of neutral endopeptidase and angiotensin-converting enzyme by sampatrilat in essential hypertension.
Clin Pharmacol Ther. 1998 Oct; 64(4):439-49.CP

Abstract

BACKGROUND

The antihypertensive response to angiotensin-converting enzyme (ACE) inhibitors may be attenuated by a compensatory decrease in atrial natriuretic factor production. If so, inhibition of atrial natriuretic factor breakdown by neutral endopeptidase (NEP) may enhance the antihypertensive effects of ACE inhibition. We compared effects of the combined ACE-NEP inhibitor sampatrilat, lisinopril, and placebo on blood pressure, plasma ACE, and renin activity and urinary cyclic guanosine monophosphate (cGMP) of patients with hypertension.

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.

Authors+Show Affiliations

University Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, England.No affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9797801

Citation

Wallis, E J., et al. "Combined Inhibition of Neutral Endopeptidase and Angiotensin-converting Enzyme By Sampatrilat in Essential Hypertension." Clinical Pharmacology and Therapeutics, vol. 64, no. 4, 1998, pp. 439-49.
Wallis EJ, Ramsay LE, Hettiarachchi J. Combined inhibition of neutral endopeptidase and angiotensin-converting enzyme by sampatrilat in essential hypertension. Clin Pharmacol Ther. 1998;64(4):439-49.
Wallis, E. J., Ramsay, L. E., & Hettiarachchi, J. (1998). Combined inhibition of neutral endopeptidase and angiotensin-converting enzyme by sampatrilat in essential hypertension. Clinical Pharmacology and Therapeutics, 64(4), 439-49.
Wallis EJ, Ramsay LE, Hettiarachchi J. Combined Inhibition of Neutral Endopeptidase and Angiotensin-converting Enzyme By Sampatrilat in Essential Hypertension. Clin Pharmacol Ther. 1998;64(4):439-49. PubMed PMID: 9797801.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combined inhibition of neutral endopeptidase and angiotensin-converting enzyme by sampatrilat in essential hypertension. AU - Wallis,E J, AU - Ramsay,L E, AU - Hettiarachchi,J, PY - 1998/11/3/pubmed PY - 1998/11/3/medline PY - 1998/11/3/entrez SP - 439 EP - 49 JF - Clinical pharmacology and therapeutics JO - Clin. Pharmacol. Ther. VL - 64 IS - 4 N2 - BACKGROUND: The antihypertensive response to angiotensin-converting enzyme (ACE) inhibitors may be attenuated by a compensatory decrease in atrial natriuretic factor production. If so, inhibition of atrial natriuretic factor breakdown by neutral endopeptidase (NEP) may enhance the antihypertensive effects of ACE inhibition. We compared effects of the combined ACE-NEP inhibitor sampatrilat, lisinopril, and placebo on blood pressure, plasma ACE, and renin activity and urinary cyclic guanosine monophosphate (cGMP) of patients with hypertension. 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. SN - 0009-9236 UR - https://www.unboundmedicine.com/medline/citation/9797801/Combined_inhibition_of_neutral_endopeptidase_and_angiotensin_converting_enzyme_by_sampatrilat_in_essential_hypertension_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0009-9236&date=1998&volume=64&issue=4&spage=439 DB - PRIME DP - Unbound Medicine ER -