Abstract P027: GCH1 and GULP1 Play a Role in Hypertension Associated With Ovarian Hormone Loss Independently of Body Weight Gain
Background and Objective: Ovarian hormone loss is associated with an increased incidence of hypertension, body weight (BW) gain and inflammation. Since BW gain is also associated with an increased incidence of hypertension, it has been difficult to separate the role of the immune system in hypertension from BW gain. Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats gain BW after ovariectomy; however, only the DS rat becomes hypertensive. In this study, we took advantage of the DS/ DR model to determine which T cell genes are associated with hypertension induced by ovarian hormone loss-independently of body weight gain.
Methods and Analysis: DS and DR rats (1 month) were either ovariectomized (OVX) or subjected to sham surgery (Sham). At 4 months of age, a microarray analysis was conducted on isolated splenic T-cells from these 4 groups and differential expression was confirmed by real-time PCR.
Results: In contrast to DR rats which remain normotensive, the mean arterial pressure (MAP) significantly increased by 14 mm Hg in DS rats after ovariectomy [MAP (mmHg): DS-OVX, 143 ± 3.4 vs DS-Sham, 129 ± 9.4; n=10-11/group; p=0.0002; DR-OVX, 123 ± 15 vs DR-Sham, 126 ± 4.8; n=11-12/group; ns]. Both rat strains, however, exhibited a similar 17-20% increase in BW after ovariectomy compared to sham treatment [BW (g): DS-OVX, 372 ± 34 vs. DS-Sham, 308 ± 13; n=6-7/group; p<0.05; DR-OVX, 323 ± 22 vs, DR-Sham, 276 ± 49; n=7/group; p<0.05]. Microarray analysis suggested that among many others, the genes GTP Cyclohydrolase 1 (GCH1) and Engulfment Adaptor PTB Domain Containing 1 (GULP1) were specifically associated with resistance or susceptibility to hypertension induced by ovarian hormone loss. Real-time PCR confirmed that GCH1 and GULP1 were selectively elevated by ovariectomy in DS but not DR splenic T cells.
Conclusion: GCH1 and GULP1 play a role in hypertension associated with ovarian hormone loss independently of BW gain, which has implications for women with ovarian hormone deficiency due to premature ovarian failure or elective oophorectomy.
Author Disclosures: A.V. Pai: None. S. Woperrer: None. H. Ji: None. X. Wu: None. J. Li: None. K. Sandberg: None.
- © 2015 by American Heart Association, Inc.