Abstract
Background: We previously reported that mineralocorticoid receptor antagonism (MRA) prevents high-salt-induced increase in blood pressure in intact male and female mice. Interesting sex differences exist with respect to blood pressure. Pre-menopausal women are protected from hypertension and cardiovascular disease compared to age-matched males. The sex steroids estrogen and testosterone are likely responsible for these sex differences. The purpose of this study was to determine if MRA also prevents high-salt-induced increase in blood pressure in gonadectomized mice.
Methods: Gonadectomized male and female CD-1 mice, 5 – 7 weeks old, were purchased from ENVIGO, Inc. Mice were placed in metabolic cages for a 5-day baseline (BL) period consuming normal food with water. After BL, either a placebo (P) or spironolactone (Sp) pellet (25mg, 21-day release, Innovative Research of America) was implanted sc and mice consumed a salt-deficient (SD) diet (Teklad, TD90228) with water for seven days. After the SD period, mice consumed a high-salt (HS) diet of 4% NaCl with 1% saline for seven days. Groups included male-P (MP), male-Sp (MSp), female-P (FP), and FSp (n=6/group). Systolic blood pressure (SBP, mmHg) was measured daily via the tail-cuff technique (CODA, Kent Scientific).
Results: In male mice, SBP did not change in the SD period in either the MP & MSp mice: (MP mice: BL vs SD: 93.2 ± 1.1 vs 95.6 ± 1.2; MSp mice: 95.6 ± 2.0 vs 101.2 ± 1.8, respectively). Also, SBP did not show significant difference when comparing SBP between the SD and HS periods: (MP mice: SD vs HS: 95.6 ± 1.9 vs 101.7 ± 4.7; and MSp mice: SD vs HS: 101.1 ± 6.4 vs 98.1 ± 1.1). In female mice, SBP was not different between the BL and SD periods in either the FP or FSp groups. (FP mice: BL vs SD: 94.7 ± 3.3 vs 100.1 ± 1.1; FSp mice, BL vs SD: 96.8.5 ± 3.8 vs 96.0 ± 2.7). SBP increased in FP mice in the HS period (FP mice, SD vs HS period 101.1 ± 1.1 vs 107.4 ± 1.1; p<0.05). SBP was not increased in the FSp mice (FSp mice: SD vs HS: 96.0 ± 2.7 vs 98.5 ± 2.7).
Conclusions: MR antagonism prevents HS-induced elevation in blood pressure in the female gonadectomized mice but not in the male gonadectomized mice. Results suggest that sex steroids estrogen and testosterone, particularly the latter play a role in regulating MRA-induced regulation of blood pressure.
Methods: Gonadectomized male and female CD-1 mice, 5 – 7 weeks old, were purchased from ENVIGO, Inc. Mice were placed in metabolic cages for a 5-day baseline (BL) period consuming normal food with water. After BL, either a placebo (P) or spironolactone (Sp) pellet (25mg, 21-day release, Innovative Research of America) was implanted sc and mice consumed a salt-deficient (SD) diet (Teklad, TD90228) with water for seven days. After the SD period, mice consumed a high-salt (HS) diet of 4% NaCl with 1% saline for seven days. Groups included male-P (MP), male-Sp (MSp), female-P (FP), and FSp (n=6/group). Systolic blood pressure (SBP, mmHg) was measured daily via the tail-cuff technique (CODA, Kent Scientific).
Results: In male mice, SBP did not change in the SD period in either the MP & MSp mice: (MP mice: BL vs SD: 93.2 ± 1.1 vs 95.6 ± 1.2; MSp mice: 95.6 ± 2.0 vs 101.2 ± 1.8, respectively). Also, SBP did not show significant difference when comparing SBP between the SD and HS periods: (MP mice: SD vs HS: 95.6 ± 1.9 vs 101.7 ± 4.7; and MSp mice: SD vs HS: 101.1 ± 6.4 vs 98.1 ± 1.1). In female mice, SBP was not different between the BL and SD periods in either the FP or FSp groups. (FP mice: BL vs SD: 94.7 ± 3.3 vs 100.1 ± 1.1; FSp mice, BL vs SD: 96.8.5 ± 3.8 vs 96.0 ± 2.7). SBP increased in FP mice in the HS period (FP mice, SD vs HS period 101.1 ± 1.1 vs 107.4 ± 1.1; p<0.05). SBP was not increased in the FSp mice (FSp mice: SD vs HS: 96.0 ± 2.7 vs 98.5 ± 2.7).
Conclusions: MR antagonism prevents HS-induced elevation in blood pressure in the female gonadectomized mice but not in the male gonadectomized mice. Results suggest that sex steroids estrogen and testosterone, particularly the latter play a role in regulating MRA-induced regulation of blood pressure.
Original language | American English |
---|---|
Pages | 95 |
State | Published - 18 Feb 2022 |
Event | Oklahoma State University Center for Health Sciences Research Week 2022 : Poster Presentation - Oklahoma State University Center for Health Sciences, Tulsa, United States Duration: 14 Feb 2022 → 18 Feb 2022 https://medicine.okstate.edu/research/docs/rw2022_agenda.pdf (Research Week 2022 Agenda) |
Conference
Conference | Oklahoma State University Center for Health Sciences Research Week 2022 |
---|---|
Country/Territory | United States |
City | Tulsa |
Period | 14/02/22 → 18/02/22 |
Internet address |
|
Keywords
- Spironolactone
- blood pressure
- Sex Steroids