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.
Ritter
J M
JM
Department of Clinical Pharmacology, UMDS, Guy's Hospital, London, UK.
Cockcroft
J R
JR
Sciberras
D G
DG
Goldberg
M R
MR
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