International Circulation:  It is known that the actions of angiotensin II contribute to a variety of cardiovascular diseases such as coronary artery disease， heart failure and hypertension.  What are the roles of the two receptors， angiotensin II type I  (AT-1) receptor and angiotensin II type II (AT-2) receptor?  Are they equally responsible for those conditions or can we favor one over the other?

Ernesto Schiffrin:  Actually AT-1 receptor is the main mediator for the actions of angiotensin II and is the main receptor involved in the pathophysiology leading to blood pressure elevation， cardiac remodeling， participating in heart failure， and contributing to the progression of chronic kidney disease.  The AT-2 receptor is in fact abundant in fetal life and is later down regulated.  It appears to again be up regulated if there is an inflammatory response and may have vascular protective effects.  We have provided some evidence for that in some conditions.  They seem to have two opposing effects， one is pathophysiological， certainly plays a role in physiology， continuing to maintain blood pressure when people are salt depleted or dehydrated.  When renin-angiotensin system is inappropriately activated then the AT-1 receptor is the one that is mediating the pathophysiological effects and perhaps AT-2 receptors are somewhat vasculo-protective， although this remains slightly controversial.