Endogenous angiotensin II and baroreceptor dysfunction: a comparative study of losartan and enalapril in man

K. M. Yee, A. D. Struthers

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    20 Citations (Scopus)

    Abstract

    Aims
    To assess the role of direct AT1 receptor antagonism in baroreceptor
    modulation in man, and to perform a direct comparison of Ang II blockade at the
    receptor level with that of ACE inhibition.

    Methods
    Ten healthy male volunteers [mean age (s.d.) 23 (6.9)] pretreated with
    frusemide therapy (40 mg day-1 for 3 days prior to each visit) were studied on 3
    separate days, 10 days apart, in a placebo-controlled, randomized, double-blind, cross-over fashion. On each study day, subjects were randomly given either a single-dose of enalapril 20 mg, losartan 50 mg or placebo. Baroreceptor function was assessed by measuring changes in blood pressure (BP), pulse interval (RR Int) and heart rate (HR) in response to incremental doses of intravenous phenylephrine infusions (0.2–3.6µg kg-1min-1).

    Results
    In response to phenylephrine, no significant differences in BP responses
    were observed with any of the study medications but reflex heart rate responses
    were significantly increased with both enalapril and losartan compared with placebo (P<0.05). The (RR/?sBP ratio, taken as a measure of baroreceptor sensitivity (BRS) was significantly increased with enalapril [12.2+4.6 ms mmHg-1
    (mean+s.d.)] and losartan [11.9+3.6 ms mmHg-1] compared with placebo
    [9.2+4.5 ms mmHg-1]; i.e. enalapril and losartan increased the (RR/(?sBP ratio
    by 3.0 ms mmHg-1 (95%CI 0.5, 5.6; P<0.05) and 2.8 ms mmHg-1(95%CI 0.6,
    5.0; P<0.038), respectively. There were however, no significant differences between losartan and enalapril [mean difference 0.25 (95%CI-1.6, 2.1)].

    Conclusions
    The present study confirms observations from animal models that
    blocking endogenous angiotensin II in man improves baroreceptor function. Both
    strategies, AT1 receptor antagonism and ACE inhibition appear to be equally
    effective in restoring baroreceptor function in salt-depleted normotensive subjects.

    Original languageEnglish
    Pages (from-to)583-8
    Number of pages6
    JournalBritish Journal of Clinical Pharmacology
    Volume46
    Issue number6
    DOIs
    Publication statusPublished - Dec 1998

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