Nitric oxide: a physiological mediator of the type 2 (AT2) angiotensin receptor.
Virtually all of the biological actions of angiotensin II (ANG II) have been thought to be mediated by the type 1 (AT1) angiotensin receptor and the function of the type 2 (AT2) receptor is unknown. We now describe a novel physiological action of ANG II to release nitric oxide (NO) mediated by the AT2 receptor in both the kidney and gastrointestinal tract. We present an integrated model for a counter-regulatory protective action of the AT2 receptor mediated by nitric oxide. In the kidney, ANG II at the AT2 receptor stimulates a vasodilator cascade of bradykinin (BK), NO and cyclic GMP which is tonically activated only during conditions of increased ANG II, such as sodium depletion. In the absence of the AT2 receptor, pressor and antinatriuretic hypersensitivity to ANG II is associated with BK and NO deficiency. In angiotensin-dependent hypertension, the hypotensive effect at AT1 receptor blockade is due at least in part to AT2 receptor stimulation and consequent increased activity of the vasodilator cascade. In the gastrointestinal tract, physiological quantities of ANG II stimulate the AT2 receptor releasing NO and cGMP leading to increased sodium and water absorption. In conclusion, NO is an important physiological mediator of ANG II at the AT2 receptor.
Carey
R M
RM
Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA.
Jin
X
X
Wang
Z
Z
Siragy
H M
HM
D000042:Absorption; D000818:Animals; D001834:Body Water / Q000378:metabolism; D001920:Bradykinin / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004064:Digestive System / Q000378:metabolism; D006978:Hypertension, Renovascular / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000172:deficiency / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology
D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D009569:Nitric Oxide; D012964:Sodium; D006152:Cyclic GMP; D001920:Bradykinin