Abstract 441: Sex Differences in Microglia Activation During Subpressor Dose of Angiotensin (Ang) II Sensitization of Subsequent Pressor Dose of Ang II
In previous studies using the Induction-Delay-Expression (I-D-E) experimental design we have shown that there are sex differences in the effects of one-week Ang II pre-treatment to sensitize the brain to produce an enhanced hypertensive response to subsequent Ang II. In other studies, we have shown that females are protected from hypertension and brain infiltration of T lymphocytes during Ang II infusion. The purpose of the present study was to test whether there is a sex difference in brain microglia activation on the sensitizing effects of Ang II. The present studies followed an I-D-E experimental design. Three male and three female Sprague-Dawley rats were assigned to each of the following experimental groups: 1) Control ( I saline + D) ; 2) I-Ang II+D ( I with subpressor dose of Ang II, 10 ng/kg/min); 3) I-saline+D+E-Ang II (I with saline plus E with a pressor dose of Ang II, 120 ng/kg/min); 4) I-Ang II+D+E-Ang II (I with subpressor dose of Ang II plus E with pressor dose of Ang II). At the end of the experiment, animals were anesthetized and perfused with formalin. Thirty-micron frozen slices of the area postrema (AP), nucleus tractus solitarius (NTS), and subfornical organ (SFO) were processed for IHC staining with IBa-1 microglia antibody (WAKO, 1:200). The number of IBa-1+ activated microglia (MG) in each region were counted in an approx 3 consecutive brain slices from 3 separate animals. The subpressor dose of Ang II resulted in a significant increase in NTS activated microglia in males (MG 19.2 vs. 5.1) but not in females (MG 1.5 vs 2.3) when compared to control. In females, the pressor dose of Ang II did not increase the activated microglia in the NTS. The numbers of activated microglia in the AP was similar in males and females in the I-Ang II+D+E-Ang II group, but in the I-Sal+D+E-Ang II, males had greater number of MG in the AP as compared to females (21.5 vs 11.8, P=0.05). The number of MG in the SFO were low across all groups compared to the number of MG in other regions examined (males I-Ang II+D+E-Ang II group averaged 3.9 MG vs females averaged 2.3 MG). These results suggest that sex differences observed in the brain sensitization to Ang II may involve differential induction of microglia activation in selective brain regions important for Ang II generation of hypertension.
Author Disclosures: M. Hay: None. F. Samareh- Jahani: None. B. Xue: None. A.K. Johnson: None.
- © 2014 by American Heart Association, Inc.