Previous studies using an Induction-Delay-Expression (I-D-E) experimental design demonstrated that pre-treatment with ANG II for 1 week produces a sensitized hypertensive response to subsequent ANG II administration in males but not in females. In this sensitization process, several brain renin-angiotensin-aldosterone system components including angiotensin converting enzyme 2 (ACE2) expressions were enhanced. It has been shown that ANG (1-7), formed from ANG II by ACE2, plays an anti-hypertensive role in the central nervous system. The present study tested whether central ANG (1-7) protects against the sensitizing effects of a low dose of ANG II.
Male and female rats were implanted for telemetered blood pressure (BP) recording. During I low doses of ANG II alone or with concurrent icv administration of ANG (1-7) or its antagonist A-779 were given for 1 week. After a 1 week rest (D ), a slow pressor dose of ANG II was given for 2 weeks (E ).
In males, the low dose of ANG II during I resulted in an enhanced pressor response to the subsequent slow pressor dose of ANG II given during E in comparison to those rats receiving vehicle during I (Δ42.8±7.2 vs Δ21.2±5.3 mmHg). Central administration of ANG (1-7) during I blocked the low dose ANG II-induced sensitization (Δ16.4±4.0 mmHg). In contrast, the low dose of ANG II did not sensitize the hypertensive response in females to the subsequent slow pressor dose of ANG II (Δ13.0±5.4 vs Δ9.9±3.4 mmHg). Central blockade of ANG (1-7) by icv infusion of A-779 during I resulted in sensitization by the low dose of ANG II (Δ26.7±2.0 mmHg) in females. The results indicate that ANG (1-7) plays a protective role during the sensitization process, especially in females, and its administration can attenuate the development of ANG II-induced hypertension in both male and female.