Clinical pharmacology of angiotensin and bradykinin in human forearm vasculature.
OBJECTIVE
Losartan inhibits the renin-angiotensin system by blockade of angiotensin II receptors, whereas enalapril blocks the renin-angiotensin system by inhibiting the conversion of angiotensin I to angiotensin II by the angiotensin converting enzyme (ACE). Since ACE inactivates bradykinin in addition to its action on angiotensin I we hypothesized that losartan and enalapril have different effects on the response to angiotensin and bradykinin.


METHODS
We studied healthy volunteers dosed with placebo, enalapril and losartan 4-6 h before measurement of forearm blood flow by venous occlusion plethysmography. Saline, angiotensin I, angiotensin II and bradykinin were infused into the left brachial artery.


RESULTS
Losartan produced a similar inhibition of the vasoconstriction induced by angiotensin I and angiotensin II without significantly influencing the bradykinin-induced vasodilation, whereas enalapril potentiated the vasodilator effect of bradykinin and selectively inhibited the vasoconstriction induced by angiotensin I without altering the response to angiotensin II.


CONCLUSIONS
These pharmacological differences suggest that angiotensin II receptor antagonists and ACE inhibitors may not be therapeutically equivalent.
Department of Clinical Pharmacology, UMDS, Guy's Hospital, London, UK.
J M
JM
Ritter
J R
JR
Cockcroft
D G
DG
Sciberras
M R
MR
Goldberg
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology*; D004656:Enalapril / Q000494:pharmacology; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A; D019808:Losartan; D001920:Bradykinin