Abstract P209: Loss Of Rgs2 Specifically In CD4+ T Cells Decreases The Hypertensive Response To Vasopressin

Regulator of G protein Signaling (RGS) family members can modulate multiple cardiovascular hormones and are associated with hypertension and preeclampsia, a hypertensive disorder in pregnancy. We previously observed a 9-fold increase in RGS2 in CD4+ T cells isolated from women with preeclampsia compared to normotensive women. Further, in non-pregnant mice, we showed that loss of RGS2 in CD4+ T cells prevented angiotensin II-induced hypertension (measured via radiotelemetry) and resulted in increased levels of the anti-inflammatory cytokines interleukin 4 and transforming growth factor beta. We hypothesize that modulating RGS2 in CD4+ T cells may be a therapeutic strategy for hypertension. The objective of this study was to determine if loss of RGS2 specifically in CD4+ T cells protects against the development of arginine vasopressin-induced hypertension in mixed background CD4+ RGS2 knockout mice (CD4 RGS2 KO ). To generate mice wherein RGS2 is specifically knocked out in CD4+ T cells, CD4-Cre+ mice (C57BL/6J) were crossed with RGS2 flox/flox mice (B6SJLF1/J). Female 8-12 week old CD4 RGS2 KO or littermate control mice (n=5 per group) from this mixed strain were administered 24 ng/hr vasopressin for 21 days via mini-osmotic pump. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MP), and heart rate (HR) were assessed using a high throughput non-invasive blood pressure system. Prior to vasopressin infusion, KO and CTL mice showed no differences in SBP, DBP, MP, or HR. At 9-13 days of vasopressin-infusion, KO mice had a significantly lower 24-hr SBP [KO 138.7 ±4.7 vs CTL 155.9 ±3.4 mmHg, p<0.05], DBP [KO 106.9 ±4.1 vs CTL 122.8 ±2.9 mmHg, p<0.05], MP [KO 117.2 ±4.3 vs CTL 133.5 ±3.0 mmHg, p<0.05], and HR [KO 378 ±18.7 vs CTL 445 x±12.8 BPM, p<0.05] compared to CTL mice. Here, we demonstrate that in a mixed strain CD4+ RGS2 KO mouse, loss of RGS2 specifically in CD4+ T cells prevented vasopressin-induced hypertension. Therefore, RGS2 expression in CD4+ T cells may play an expanded role in the modulation of hypertension.