EFFECTS OF PREGNANCY AND PROGESTERONE METABOLITES ON ARTERIAL BAROREFLEX IN CONSCIOUS RATS

Previous experiments in anesthetized rats suggested that sympathoexcit atory responses were attenuated in pregnant (P) rats. The major proges terone metabolite, 3 alpha-hydroxy-dihydroprogesterone (3 alpha-OH-DHP ), is elevated in pregnancy and reportedly potentiates central gamma-a minobutyric acidergic mechanisms, whereas the 3 beta-isomer (3 beta-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 pressu re (MAP) [iv phenylephrine (PE) and nitroprusside (NTP)] in P rats and in virgin (V) rats before (control) and 15 min after infusion (iv) of 3 alpha-OH-DHP or 3 beta-OH-DHP. Baseline MAP was lower in P rats (P = 102 +/- 2 vs. V = 124 +/- 3 mmHg). Compared with V rats, P rats exhi bited less ''sympathetic reserve'' to respond to a hypotensive challen ge, as evidenced by decreased maximum NA and decreased slope of RSNA b aroreflex responses to NTP. However, HR baroreflex curves were similar in P and V rats. Acute intravenous administration of 3 alpha-OH-DHP t o conscious V rats mimicked the effects of pregnancy. Baroreflex sympa thoexcitatory responses were decreased, whereas baroreflex control of HR was unaffected. The 3 beta-isomer of DHP had no effect on NA or HR baroreflex responses. These results suggest that pregnancy may have di fferential effects on baroreflex control of sympathetic outflow and HR , and the major metabolite of progesterone, 3 alpha-OH-DHP, may contri bute to this adaptation of pregnancy.