Angiotensin II type 2 receptor-mediated vasodilation. Focus on bradykinin, NO and endothelium-derived hyperpolarizing factor(s).
Angiotensin (Ang) II type 1 (AT(1)) receptors account for the majority of the cardiovascular effects Ang II, including vasoconstriction and growth stimulation. Recent evidence, mainly obtained in animals, suggests that Ang II type 2 (AT(2)) receptors counteract some or all of these effects. This review summarizes the current knowledge on the vasodilator effects induced by AT(2) receptors in humans and animals, focussing not only on the mediators of this effect, but also on the modulatory role of age, gender, and endothelial function. It is concluded that AT(2) receptor-mediated vasodilation most likely depends on the bradykinin-bradykinin type 2 (B(2)) receptor-NO-cGMP pathway, although evidence for a direct link between AT(2) and B(2) receptors is currently lacking. If indeed B(2) receptors are involved, this would imply that, in addition to NO, also the wide range of non-NO 'endothelium-derived hyperpolarizing factors' (EDHFs) that is released following B(2) receptor activation (e.g., K(+), cytochrome P450 products from arachidonic acid, H(2)O(2) and S-nitrososothiols), could contribute to AT(2) receptor-induced vasodilation.
Batenburg
Wendy W
WW
Department of Pharmacology, room EE1418b, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Tom
Beril
B
Schuijt
Martin P
MP
Danser
A H Jan
AH
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D001920:Bradykinin / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001685:Biological Factors; D044139:Receptor, Angiotensin, Type 2; C067410:endothelium-dependent hyperpolarization factor; D000804:Angiotensin II; D009569:Nitric Oxide; D001920:Bradykinin