AT(2) Receptors: Potential Therapeutic Targets for Hypertension

作者：Carey Robert M

来源：American Journal of Hypertension, 2017, 30(4): 339-347.

DOI：10.1093/ajh/hpw121

• angiotensin receptors
• angiotensin II infusion model
• antihypertensive agent
• AT(2) receptor activation
• blood pressure
• cell signaling
• experimental hypertension
• hypertension
• natriuresis
• receptor trafficking
• sodium excretion
• sodium transporters
• sodium-hydrogen exchanger-3
• sodium-potassium/ATPase
• treatment of hypertension

The renin-angiotensin system (RAS) is arguably the most important and best studied hormonal system in the control of blood pressure (BP) and the pathogenesis of hypertension. The RAS features its main effector angiotensin II (Ang II) acting via its 2 major receptors, angiotensin type-1(AT(1)R) and type-2 (AT(2)R). In general, AT(2)Rs oppose the detrimental actions of Ang II via AT(1)Rs. AT(2)R activation induces vasodilation and natriuresis, but its effects to lower BP in hypertension have not been as clear as anticipated. Recent studies, however, have demonstrated that acute and chronic AT(2)R stimulation can induce natriuresis and lower BP in the Ang II infusion model of experimental hypertension. AT(2)R activation induces receptor recruitment from intracellular sites to the apical plasma membranes of renal proximal tubule cells via a bradykinin, nitric oxide, and cyclic guanosine 3',5' monophosphate signaling pathway that results in internalization and inactivation of sodium (Na+) transporters Na+-H+ exchanger-3 and Na+/K+ ATPase. These responses do not require the presence of concurrent AT(1)R blockade and are effective both in the prevention and reversal of hypertension. This review will address the role of AT(2)Rs in the control of BP and Na+ excretion and the case for these receptors as potential therapeutic targets for hypertension in humans.

• 出版日期2017-4