Role of Serotonin in the Nucleus of the Solitary Tract on Arterial Blood Pressure Regulation

Hypertension affects nearly half of adults in the U.S. and can be a major risk factor for cardiovascular disease. Serotonin (5-Hydroxytryptamine; 5-HT) neurons project widely to cardiorespiratory nuclei in the brainstem. We previously showed that a loss of central 5-HT in adult male rats led to an increase in arterial blood pressure (ABP) while in females the effect was variable and not significantly different than controls. Here, we investigated the extent that 5-HT acts within the nucleus of the solitary tract (nTS) to maintain ABP of adult male and female rats. We hypothesized that silencing nTS-projecting 5-HT neurons increases the ABP of males with a smaller, more variable effect in females that depends on estrus cycle stage. The nTS of adult male (n=5) and female (n=2) LE- Tph2 tm1(cre) rats was injected with a Cre-dependent, retrogradely-transported adeno-associated virus expressing inhibitory Designer Receptors Exclusively Activated by Designer Drugs (Gi-DREADDs) to allow silencing of projecting 5-HT neurons. We implanted arterial and venous catheters for measuring ABP, heart rate (HR), and for delivery of vehicle or Compound 21 (C21; 1 mg/kg) to activate the Gi-DREADD. Following 1 week recovery and acclimation to plethysmography chamber, each rat was tested with both C21 and vehicle, with 1 week between experiments. Female rats were estrous staged by vaginal cytology prior to experiments. On the experimental day, we recorded breathing, ABP and HR for 1 hr, and then injected ~100ul of vehicle or C21 and monitored cardiorespiratory variables for another 1 hr. Gi-DREADD activation induced a marked, rapid (within 20 sec) increase in mean arterial pressure (MAP) of males (~30 mmHg; p<0.001) with no significant change in HR. In females – one in diestrus and the other in estrus – the effect of silencing serotonergic projections to nTS was much smaller, with ABP increasing 4.8 and 7.5 mmHg, respectively. These data suggest that serotonergic projections to the nTS maintain ABP within normal limits by constraining sympathetic drive to the vasculature, a concept that will be tested in future experiments. Future experiments will also continue to address the possibility that in females, serotonergic inputs to the nTS have a more modest influence on ABP that depends on female sex hormones. This study was funded by grant R01HL136710 (NHLBI; Cummings (MPI)). This abstract was presented at the American Physiology Summit 2025 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.