Combined inhibition of neutral endopeptidase and angiotensin-converting enzyme by sampatrilat in essential hypertension

被引:45
作者
Wallis, EJ
Ramsay, LE
Hettiarachchi, J
机构
[1] Univ Sheffield, Dept Med & Pharmacol, Royal Hallamshire Hosp, Sect Clin Pharmacol & Therapeut, Sheffield S10 2JF, S Yorkshire, England
[2] Pfizer Ltd, Sandwich, Kent, England
关键词
D O I
10.1016/S0009-9236(98)90075-3
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 ann 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.
引用
收藏
页码:439 / 449
页数:11
相关论文
共 20 条
  • [11] EFFECTS OF LOW-DOSE INFUSION OF ATRIAL-NATRIURETIC-FACTOR ON ACUTE INHIBITION OF ANGIOTENSIN CONVERTING ENZYME IN NORMAL MAN
    NAKAMURA, M
    ARAKAWA, N
    KAWATA, Y
    KATO, M
    [J]. CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 1990, 17 (01) : 17 - 22
  • [12] CANDOXATRIL, AN ORALLY ACTIVE NEUTRAL ENDOPEPTIDASE INHIBITOR, RAISES PLASMA ATRIAL-NATRIURETIC-FACTOR AND IS NATRIURETIC IN ESSENTIAL-HYPERTENSION
    OCONNELL, JE
    JARDINE, AG
    DAVIDSON, G
    CONNELL, JMC
    [J]. JOURNAL OF HYPERTENSION, 1992, 10 (03) : 271 - 277
  • [13] CHRONIC INHIBITION OF ENDOPEPTIDASE 24.11 IN ESSENTIAL-HYPERTENSION - EVIDENCE FOR ENHANCED ATRIAL-NATRIURETIC-PEPTIDE AND ANGIOTENSIN-II
    RICHARDS, AM
    WITTERT, GA
    CROZIER, IG
    ESPINER, EA
    YANDLE, TG
    IKRAM, H
    FRAMPTON, C
    [J]. JOURNAL OF HYPERTENSION, 1993, 11 (04) : 407 - 416
  • [14] RICHARDS AM, 1985, LANCET, V1, P545
  • [15] DIETARY-SODIUM AND INHIBITION OF NEUTRAL ENDOPEPTIDASE 24.11 IN ESSENTIAL-HYPERTENSION
    SINGER, DRJ
    MARKANDU, ND
    BUCKLEY, MG
    MILLER, MA
    SAGNELLA, GA
    MACGREGOR, GA
    [J]. HYPERTENSION, 1991, 18 (06) : 798 - 804
  • [16] ANTIHYPERTENSIVE AND HYPOTENSIVE EFFECTS OF ATRIAL NATRIURETIC FACTOR IN MEN
    WEDER, AB
    SEKKARIE, MA
    TAKIYYUDDIN, M
    SCHORK, NJ
    JULIUS, S
    [J]. HYPERTENSION, 1987, 10 (06) : 582 - 589
  • [17] PLASMA-LEVELS AND CARDIOVASCULAR, ENDOCRINE, AND EXCRETORY EFFECTS OF ATRIAL-NATRIURETIC-PEPTIDE DURING DIFFERENT SODIUM INTAKES IN MAN
    WEIDMANN, P
    HELLMUELLER, B
    UEHLINGER, DE
    LANG, RE
    GNAEDINGER, MP
    HASLER, L
    SHAW, S
    BACHMANN, C
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1986, 62 (05) : 1027 - 1036
  • [18] EFFECT OF DOSE ADJUSTMENT ON ENALAPRIL-INDUCED COUGH AND THE RESPONSE TO INHALED CAPSAICIN
    YEO, WW
    HIGGINS, KS
    FOSTER, G
    JACKSON, PR
    RAMSAY, LE
    [J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1995, 39 (03) : 271 - 276
  • [19] YEO WW, 1991, Q J MED, V80, P763
  • [20] YEO WW, 1990, J HUM HYPERTENS, V4, P517