All AT1 receptor antagonists have adverse effects that are not significantly different from those of a placebo, although first-dose hypotension may occur. Unlike ACE inhibitors, AT1 receptor antagonists do not produce a cough, suggesting that this side effect may be related to the buildup of bradykinin levels that occurs as a result of converting enzyme inhibition rather than to a reduction in angiotensin II levels. An additional difference between AT1 receptor antagonists and ACE inhibitors is that angiotensin II is capable of interacting at the AT2 receptor in patients treated with an AT1 receptor antagonist (but not following inhibition of ACE). The clinical significance of this difference is not understood.
Finally, additional enzymes have been identified that are capable of forming angiotensin II from angiotensin I, suggesting that inhibition of ACE may not be sufficient for the total elimination of angiotensin II. In contrast, AT1 receptor antagonists are capable of blocking the effects of angiotensin II regardless of its enzymatic route of formation. All AT1 receptor antagonists, like the ACE inhibitors, are contraindicated during pregnancy.
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