Endogenous angiotensin II and baroreceptor dysfunction: a comparative study of losartan and enalapril in man.
OBJECTIVE
To assess the role of direct ATI 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 (0.2-3.6 microg kg(-1) min(-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/AsBP ratio, taken as a measure of baroreceptor sensitivity (BRS) was significantly increased with enalapril 112.2+4.6 ms mmHg (mean+s.d.)] and losartan [11.9+3.6msmmHg(-1)] compared with placebo [9.2+4.5 ms mmHg(-1)]; i.e. enalapril and losartan increased the (RR/(delta 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, ATI receptor antagonism and ACE inhibition appear to be equally effective in restoring baroreceptor function in salt-depleted normotensive subjects.
Yee
K M
KM
University Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee.
Struthers
A D
AD
D000328:Adult; D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004656:Enalapril / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D004656:Enalapril; D019808:Losartan