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The neurosteroid metabolite of progesterone, 3α‐OH‐dihydroprogesterone (3α‐OH‐DHP), is required for attenuated baroreflex mediated sympathoexcitation in pregnancy
Author(s) -
Phaup J. Glenn,
Hasser Eileen M.,
Heesch Cheryl M.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1118.38
Subject(s) - baroreflex , endocrinology , medicine , phenylephrine , chemistry , reflex , mean arterial pressure , anesthesia , blood pressure , heart rate
Exogenous 3á‐OH‐DHP mimics effects of pregnancy on arterial baroreflex (BX) control of renal sympathetic nerve activity (RSNA). Current experiments chronically blocked endogenous 3á‐OH‐DHP formation (Finasteride administration) and evaluated BX function in NP and near‐term pregnant (P, d21) rats. Either vehicle (Veh) or Finasteride (Fin, 25mg/kg) was given daily (s.cu.) for 7 days. RSNA electrodes were implanted on d5 of treatment. On d7, reflex changes in RSNA to increases (phenylephrine, iv) and decreases (nitroprusside, iv) in mean arterial pressure (MAP) were obtained in conscious rats and data fit to a logistic curve. As seen previously, in Veh treated P rats maximum RSNA was decreased (Veh‐P, 155 ± 14%; Veh‐NP, 335 ± 44% baseline), and baroreflex curve midpoint was shifted to lower MAP (Veh‐NP, 100 ± 4; Veh‐P, 84 ± 5 mmHg). Chronic Finasteride had no effect on BX function in Veh‐NP rats, but restored maximum RSNA in P rats (Fin‐P, 309 ± 25% baseline) to NP levels, while curve midpoint remained low (Fin‐P, 74 ± 3 mmHg). Thus, 3á‐OH‐DHP, likely through positive modulation of GABAA receptors in the RVLM, contributes to attenuated BX sympathoexcitation in P rats. NIH R01 HL091164 (CMH)