The Effects of Pregnancy on the Sympathoexcitatory and Pressor Responses to Nanoinjection of Angiotensin II into the Arcuate Nucleus
Authors: Shi Zhigang , Bonillas Alyssa , Brooks Virginia L. 
Published: April 2020

Pregnancy induces profound increases in sympathetic nerve activity (SNA). Angiotensin II (AngII) may contribute, since systemic or central blockade of AngII production or receptors (AT1aR) decreases SNA in pregnant animals. However, the brain sites involved are unknown. One possibility is the arcuate nucleus (ArcN), since AngII binds to ArcN AT1aR to increase SNA, and the ArcN is a well‐established reproductive integrating center. To begin to test this hypothesis, we measured the changes in SNA and mean arterial pressure (MAP) in response to bilateral nanoinjections of AngII (30 pmol in 30 nL) into the ArcN of α‐chloralose anesthetized pregnant rats and virgin rats throughout the estrus cycle. ArcN AngII slowly increased (P<0.05) lumbar SNA (LSNA) in pregnant rats (by 50±10 % after 90 min; n=6), and the rise was larger than in proestrus rats (‐1±8 %; n=5; P<0.05), similar to diestrus rats (40±9 %; n=4), but less than estrus rats (72±12 %; n=6; P<0.05). ArcN AngII rapidly increased (P<0.05) MAP by ~10 mmHg (after 10 min) in all groups, but after 90 min the increase was sustained (P<0.05) only in pregnant (13±2 mmHg) and estrus (11±4 mmHg) rats. A cohort of ArcN neurons projects to and stimulates vasopressinergic neurons in the hypothalamic paraventricular and supraoptic nuclei. Therefore, to test if the initial or sustained increases in MAP were mediated by vasopressin, another set of estrus and pregnant rats were pretreated with the Manning Compound (V1x; 5 μg iv) 15 min before ArcN AngII. In estrus rats (n=4), V1x had no effects on baseline LSNA or MAP, but completely blocked the initial rise in MAP induced by ArcN AngII (2±3 mmHg). Nevertheless, the increase in MAP at 90 min was unchanged (13±3 mmHg; P<0.05). The LSNA response to ArcN AngII (83±9 %) was also not altered. In pregnant rats pretreated with V1x (n=4), baseline MAP decreased (P<0.05) by 10±1 mmHg, and again ArcN AngII failed to increase MAP initially (2±1 mmHg). However, the increase in MAP 90 min after ArcN AngII (7±2 mmHg) was the same as the increase 90 min after injection of artificial cerebrospinal fluid into the ArcN of V1x‐treated pregnant rats (5±2 mmHg). Again, the increase in LSNA to ArcN AngII was unchanged (30±6 %). Finally, RNAScope was used to assay AT1aR mRNA expression in the ArcN in diestrus, proestrus, and pregnant rats. ArcN AT1aR were undetectable in proestrus rats and were expressed at low but detectable levels in diestrus rats. In contrast, pregnancy markedly increased the expression of AT1aR in the ArcN. In summary, during pregnancy, ArcN AngII produces substantial increases in LSNA in association with elevated AT1aR expression. Moreover, the increase in MAP in response to ArcN AngII was reduced or eliminated in estrus and pregnant rats pretreated with a vasopressin V1 receptor blocker. In conclusion, these data highlight the ArcN as a potential site at which AngII increases SNA during normal pregnancy. The data also suggest that AngII can elicit an increase in vasopressin secretion via an action in the ArcN and that vasopressin contributes to the pressor responses induced by ArcN AngII in both estrus and pregnant rats.

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HL128181