Chemogenetic silencing of nTS serotonergic neurons significantly increased mean arterial pressure in ovariectomized female rats, but not during proestrus or estrus.
In a female rat model, sex hormones appear to protect against elevated arterial blood pressure caused by a loss of serotonergic drive to the nucleus tractus solitarius.
Hypertension is associated with several cardiovascular diseases, including heart failure and stroke, leading killers in the USA. Men are more likely to develop hypertension, but after menopause, the incidence of hypertension becomes higher in women. In many studies using anesthetized male animals, serotonin (5-hydroxytryptamine; 5-HT) has been shown to influence arterial blood pressure regulation. We previously demonstrated that chemogenetic inhibition of serotonergic neurons innervating the nucleus tractus solitarius (nTS) produces a large pressor response in males. In contrast, in females, the effect was not significantly different from that of the controls. Herein, we hypothesize that in females, nTS serotonergic neurons regulate arterial blood pressure in a sex hormone-dependent manner. We tested female rats expressing Cre-recombinase exclusively in 5-HT neurons (Tph2-Cre) that received a Cre-dependent, retrogradely transported adeno-associated virus in the nTS expressing inhibitory designer receptors exclusively activated by designer drugs (Gi-DREADDs) to selectively silence projecting 5-HT neurons. Arterial pressure and heart rate (HR) were recorded following administration of vehicle or compound 21 (C21; 1 mg/kg) during proestrus or estrus (p/estrus), and again after ovariectomy (post-OVX). During p/estrus, MAP was not significantly affected by silencing serotonergic terminals in the nTS. In contrast, post-OVX there was a significant increase in MAP following silencing, with no change in HR. ELISA confirmed that estrogen and progesterone levels were significantly reduced post-OVX compared to p/estrus. These findings suggest that female sex hormones protect against elevated arterial blood pressure caused by a loss of serotonergic drive to the nTS. Future studies will assess potential interactions between female sex hormones and 5-HT in the nTS on sympathetic nerve activity. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Farmanabadi et al. (Fri,) conducted a other in Arterial blood pressure regulation. Chemogenetic silencing of nTS projecting 5-HT neurons (Gi-DREADDs + C21) vs. Vehicle was evaluated on Mean arterial pressure (MAP) and heart rate (HR). Chemogenetic silencing of nTS serotonergic neurons significantly increased mean arterial pressure in ovariectomized female rats, but not during proestrus or estrus.
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