Loss of Angiotensin II Type 2 Receptor Improves Blood Pressure in Elastin Insufficiency.

There is ample evidence supporting a role for angiotensin II type 2 receptor (ATR) in counterbalancing the effects of angiotensin II (ang II) through the angiotensin II type 1 receptor by promoting vasodilation and having anti-inflammatory effects. Elastin insufficiency in both humans and mice results in large artery stiffness and systolic hypertension. Unexpectedly, mesenteric arteries from elastin insufficient ( ) mice were shown to have significant vasoconstriction to ATR agonism suggesting that ATR may have vasoconstrictor effects in elastin insufficiency. Given the potential promise for the use of ATR agonists clinically, the goal of this study was to determine whether ATR has vasoconstrictive effects in elastin insufficiency . To avoid off-target effects of agonists and antagonists, mice lacking ATR ( ) were bred to mice and cardiovascular parameters were assessed in wild-type (WT), , , and littermates. As previously published, mice were normotensive at baseline and had no large artery stiffness, while mice exhibited systolic hypertension and large artery stiffness. Loss of ATR in mice did not affect large artery stiffness or arterial structure but resulted in significant reduction of both systolic and diastolic blood pressure. These data support a potential vasocontractile role for ATR in elastin insufficiency. Careful consideration and investigation are necessary to determine the patient population that might benefit from the use of ATR agonists.