Clinical pharmacology of angiotensin and bradykinin in human forearm vasculature

Hypothesis: 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 6h 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. Conclusion: These pharmacological differences suggest that angiotensin II receptor antagonists and ACE inhibitors may not be therapeutically equivalent.