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In term pregnant rats, baseline GABAergic inhibition of the RVLM is increased, while baseline GABAergic inhibition of the hypothalamic paraventricular nucleus (PVN) is decreased. The major metabolite of progesterone, 3α‐hydroxy‐dihydroprogesterone (3α‐OH‐DHP), is a potent endogenous positive modulator of GABAA receptors and CNS levels of this neurosteroid are increased in pregnancy. Local regulation of the enzymes responsible for formation of 3α‐OH‐DHP, 5α‐reductase (5α‐RDA) and 3α‐hydroxysteroid dehydrogenase (3α‐HSD), is one factor which determines brain region specific actions of 3α‐OH‐DHP. Expression of mRNA for 5α‐RDA and 3α‐HSD (reference gene = MAPK) was determined in tissue punches of the RVLM and PVN from nonpregnant (NP) and term pregnant (P) rats. In the PVN, pregnancy did not change relative expression of 5α‐RDA [NP(7)= 1.0 ±0.23; P(7)= 0.64± 0.15] or 3α‐HSD [NP(5)= 1.0 ±0.38; P(6)= 0.84± 0.23]. In the RVLM, expression of 3α‐HSD [NP(5)= 1.0 ±0.54; P(6)= 0.67± 0.44] was not different between NP and P rats. However, there was a strong trend for increased expression of 5α‐RDA in P (5) [2.44± 0.89] compared to NP(5) [1.0 ±0.28] rats. Although preliminary, these data suggest that increased expression of 5α‐RDA in the RVLM of pregnant rats, could result in increased formation of the major metabolite of progesterone and potential positive modulation of GABAA receptors. (NIH HL 36245)

Previously we reported that pressor and sympathetic nerve activity (SNA) responses due to AT1 receptor activation in the SFO are potentiated in term pregnant (P) compared to nonpregnant (NP) rats. The pathway requires ionotropic glutamate receptors (iGluRs) in the PVN and rostral ventrolateral medulla (RVLM) in both P and NP rats. AT1 receptors in the PVN and RVLM contribute to potentiated responses to SFO activation in P rats. Since the PVN is obligatory to this pathway, and PVN to RVLM projections are almost exclusively glutamatergic, we considered that the enhanced role of A II in the RVLM might be related to an A II dependent increase in excitatory drive from the PVN, which could then stimulate local production of A II in the RVLM. In sinoaortic denervated inactin anesthetized rats, increases in mean arterial pressure (MAP) and lumbar SNA (LSNA) due to microinjected A II (50 nl, 1.6 mM) in the PVN were greater in P (n = 4) compared to NP (n = 7) rats (ΔMAP: P= 25±5 mmHg; NP= 15±2 mmHg; ΔLSNA: P= 13±3%; NP= 6.5±2%). Real‐time RT‐PCR was used to assess relative expression of AT1 receptor mRNA (reference gene = GAPDH) in PVN tissue punches from 5 P and 5 NP rats. Expression of AT1 receptors in the PVN tended (P = 0.1) to be greater in P (2.4±0.82) compared to NP rats (1.0±0.22). These results are consistent with an increased role of PVN AT1 receptors in sympathoexcitation in pregnancy. (NIH HL 091164)

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