Effect of angiotensin II type 1 receptor antagonism on endothelial function: role of bradykinin and nitric oxide.
BACKGROUND
The important role of the endothelium for regulation of vascular tone, growth, inflammatory response, coagulation and thrombocyte adhesion has now been recognized. Endothelial function has largely been assessed as endothelium-dependent vasodilation, assuming that endothelium-dependent vasomotion represents a surrogate marker for other important endothelial functions. An important rational for this approach has been the observation that both endothelium-dependent vasomotion and other protective endothelial functions are at least partially mediated by nitric oxide. Accumulating clinical studies have now demonstrated a close and independent association of impaired endothelium-dependent vasodilation with cardiovascular events and prognosis. These findings have stimulated interest in treatment options to improve endothelial function in patients at high cardiovascular risk.


CONCLUSIONS
This article describes recent insights into endothelial effects of both angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 (AT1) receptor blockade, which have both been shown to improve endothelial function (i.e. by increasing endothelial nitric oxide availability via bradykinin-dependent endothelial nitric oxide release). ACE has a high affinity for bradykinin and degrades the peptide, so ACE inhibition may increase bradykinin-dependent effects by preventing bradykinin degradation. Interestingly, AT1-receptor blockade appears to stimulate the bradykinin-nitric oxide pathway by increased angiotensin II type 2 receptor activation. Moreover, both treatment strategies prevent increased inactivation of endothelial nitric oxide by oxygen radicals, by reducing AT1-receptor-dependent activation of the oxidant enzyme NADPH oxidase and increasing the activity of the vascular antioxidant enzyme extracellular superoxide dismutase. These beneficial effects of ACE inhibition and AT1-receptor blockade are likely to contribute to their effects on cardiovascular events.
Landmesser
Ulf
U
Abteilung Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.
Drexler
Helmut
H
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019255:NADPH Oxidases / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D043782:Receptor, Bradykinin B2 / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D043782:Receptor, Bradykinin B2; D009569:Nitric Oxide; D019255:NADPH Oxidases; D001920:Bradykinin