The progesterone metabolite 3alpha-OH-DHP contributes to the adaptation of pregnancy by attenuating baroreflex control of sympathetic outflow without affecting heart rate.
Previous experiments in anesthetized rats suggested that sympathoexcitatory responses were attenuated in pregnant (P) rats. The major progesterone metabolite, 3alpha-hydroxy-dihydroprogesterone (3alpha-OH-DHP), is elevated in pregnancy and reportedly potentiates central gamma-aminobutyric acidergic mechanisms, whereas the 3beta-isomer (3beta-OH-DHP) is inactive. This study obtained baroreflex curves in conscious rats by recording reflex changes in renal sympathetic nerve activity (RSNA) and heart rate (HR) due to perturbations in mean arterial pressure (MAP) i.v. phenylephrine (PE) and nitroprusside (NTP) in P rats and in virgin (V) rats before (control) and 15 min after infusion (i.v.) of 3alpha-OH-DHP or 3beta-OH-DHP. Baseline MAP was lower in P rats (P = 102 +/- 2 vs. V = 124 +/- 3 mmHg). Compared with V rats, P rats exhibited less "sympathetic reserve" to respond to a hypotensive challenge, as evidenced by decreased maximum NA and decreased slope of RSNA baroreflex responses to NTP. However, HR baroreflex curves were similar in P and V rats. Acute intravenous administration of 3alpha-OH-DHP to conscious V rats mimicked the effects of pregnancy. Baroreflex sympathoexcitatory responses were decreased, whereas baroreflex control of HR was unaffected. The 3beta-isomer of DHP had no effect on NA or HR baroreflex responses. These results suggest that pregnancy may have differential effects on baroreflex control of sympathetic outflow and HR, and the major metabolite of progesterone, 3alpha-OH-DHP, may contribute to this adaptation of pregnancy.
Masilamani et al. (Sat,) studied this question.