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

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.