Alleviating Hypertension by Selectively Targeting Angiotensin Receptor-Expressing Vagal Sensory Neurons.

Cardiovascular homeostasis is maintained, in part, by neural signals arising from arterial baroreceptors that apprise the brain of blood volume and pressure. Here, we test whether neurons within the nodose ganglia that express angiotensin type-1a receptors (referred to as NGAT1aR) serve as baroreceptors that differentially influence blood pressure (BP) in male and female mice. Using Agtr1a-Cre mice and Cre-dependent AAVs to direct tdTomato to NGAT1aR, neuroanatomical studies revealed that NGAT1aR receive input from the aortic arch, project to the caudal nucleus of the solitary tract (NTS), and synthesize mechanosensitive ion channels, Piezo1/2 To evaluate the functionality of NGAT1aR, we directed the fluorescent calcium indicator (GCaMP6s) or the light-sensitive channelrhodopsin-2 (ChR2) to Agtr1a-containing neurons. Two-photon intravital imaging in Agtr1a-GCaMP6s mice revealed that NGAT1aR couple their firing to elevated BP, induced by phenylephrine (i.v.). Furthermore, optical excitation of NGAT1aR at their soma or axon terminals within the caudal NTS of Agtr1a-ChR2 mice elicited robust frequency-dependent decreases in BP and heart rate, indicating that NGAT1aR are sufficient to elicit appropriate compensatory responses to vascular mechanosensation. Optical excitation also elicited hypotensive and bradycardic responses in ChR2-expressing mice that were subjected to deoxycorticosterone acetate (DOCA)-salt hypertension; however, the duration of these effects was altered, suggestive of hypertension-induced impairment of the baroreflex. Similarly, increased GCaMP6s fluorescence observed after administration of phenylephrine was delayed in mice subjected to DOCA-salt or chronic delivery of angiotensin II. Collectively, these results reveal the structure and function of NGAT1aR and suggest that such neurons may be exploited to discern and relieve hypertension.

Reducing Fear to Help Build Healthy Families: Investing in Non-Punitive Approaches to Helping People with Substance Use Disorder.

BACKGROUND: Many pregnant and parenting people with substance use disorders (SUD) refrain from seeking perinatal care or treatment for their SUD for fear of being treated poorly by health care providers and/or triggering a child welfare investigation. For those who do seek treatment, there are relatively few clinicians willing and able to prescribe medications for opioid use disorder (MOUD) to pregnant people. Both stigma and lack of access to treatment put many pregnant and parenting people at risk. Drug-related deaths contribute significantly to U.S. maternal mortality rates, with people at especially high risk of drug overdose in the months following delivery. METHODS: The Foundation for Opioid Response Efforts (FORE) is a national philanthropy focused on finding and fostering solutions to the opioid crisis. We draw lessons from our grantees' efforts to expand access to substance use treatment and recovery supports for pregnant and parenting people. RESULTS: To build systems of care that ensure more pregnant people get timely perinatal care, we need to expand training for perinatal providers on how to provide OUD treatment, clarify child welfare reporting rules, and engage and support trusted organizations and community-based services. CONCLUSIONS: In addition to changes to our systems of SUD treatment and recovery, we need greater philanthropic investment in efforts to combat the public health crisis of substance use and overdose among pregnant and parenting people. Private funders have the leeway to act quickly, take risks, and demonstrate the effectiveness of new approaches, building the case for investment of public resources in such initiatives.

Mechanosensation of the heart and gut elicits hypometabolism and vigilance in mice.

Interoception broadly refers to awareness of one's internal milieu. Vagal sensory afferents monitor the internal milieu and maintain homeostasis by engaging brain circuits that alter physiology and behavior. While the importance of the body-to-brain communication that underlies interoception is implicit, the vagal afferents and corresponding brain circuits that shape perception of the viscera are largely unknown. Here, we use mice to parse neural circuits subserving interoception of the heart and gut. We determine vagal sensory afferents expressing the oxytocin receptor, hereafter referred to as NDGOxtr, send projections to the aortic arch or stomach and duodenum with molecular and structural features indicative of mechanosensation. Chemogenetic excitation of NDGOxtr significantly decreases food and water consumption, and remarkably, produces a torpor-like phenotype characterized by reductions in cardiac output, body temperature, and energy expenditure. Chemogenetic excitation of NDGOxtr also creates patterns of brain activity associated with augmented hypothalamic-pituitary-adrenal axis activity and behavioral indices of vigilance. Recurrent excitation of NDGOxtr suppresses food intake and lowers body mass, indicating that mechanosensation of the heart and gut can exert enduring effects on energy balance. These findings suggest that the sensation of vascular stretch and gastrointestinal distention may have profound effects on whole body metabolism and mental health.

Community Support Persons and Mitigating Obstetric Racism During Childbirth.

PURPOSE: We undertook a study to assess whether presence of community support persons (CSPs), with no hospital affiliation or alignment, mitigates acts of obstetric racism during hospitalization for labor, birth, and immediate postpartum care. METHODS: We conducted a cross-sectional cohort study, measuring 3 domains of obstetric racism as defined for, by, and with Black birthing people: humanity (violation of safety and accountability, autonomy, communication and information exchange, and empathy); kinship (denial or disruption of community and familial bonds that support Black birthing people); and racism in the form of anti-Black racism and misogynoir (weaponization of societal stereotypes and scripts in service provision that reproduce gendered anti-Black racism in the hospital). We used a novel, validated instrument, the Patient-Reported Experience Measure of Obstetric Racism (the PREM-OB Scale suite), and linear regression analysis to determine the association between CSP presence during hospital births and obstetric racism. RESULTS: Analyses were based on 806 Black birthing people, 720 (89.3%) of whom had at least 1 CSP present throughout their labor, birth, and immediate postpartum care. The presence of CSPs was associated with fewer acts of obstetric racism across all 3 domains, with statistically significant reductions in scores in the CSP group of one-third to two-third SD units relative to the no-CSP group. CONCLUSIONS: Our findings suggest that CSPs may be an effective way to reduce obstetric racism as part of quality improvement initiatives, emphasizing the need for democratizing the birthing experience and birth space, and incorporating community members as a way to promote the safety of Black birthing people in hospital settings.Annals "Online First" article.

Clinicians' Perspectives on Racism and Black Women's Maternal Health.

Objective: The objective of this study was to explore clinician perceptions of how racism affects Black women's pregnancy experiences, perinatal care, and birth outcomes. Materials and Methods: We conducted 25 semi-structured interviews with perinatal care clinicians practicing in the San Francisco Bay Area (January to March 2019) who serve racially diverse women. Participants were primarily recruited through "Dear Perinatal Care Provider" email correspondences sent through department listservs. Culturally concordant, qualitatively trained research assistants conducted all interviews in person. The interviews ranged from 30 to 60 minutes and were audio-recorded and professionally transcribed verbatim. We used the constant comparative method consistent with grounded theory to analyze data. Results: Most participants were obstetrician/gynecologists (n = 11, 44%) or certified nurse midwives (n = 8, 32%), had worked in their current role for 1 to 5 years (n = 10, 40%), and identified as white (n = 16, 64%). Three themes emerged from the interviews: provision of inequitable care (e.g., I had a woman who had a massive complication during her labor course and felt like she wasn't being treated seriously); surveillance of Black women and families (e.g., A urine tox screen on the Black baby even though it was not indicated, and they didn't do it on the white baby when, in fact, it was indicated); and structural care issues (e.g., the history of medical racial experimentation). Conclusion: Clinicians' views about how racism is currently operating and negatively impacting Black women's care experiences, health outcomes, and well-being in medical institutions will be used to develop a racial equity training for perinatal care clinicians in collaboration with Black women and clinicians.

Destigmatizing and Democratizing Postpartum Care: A "Black Woman-Person First" Approach.

Optimizing postpartum care highlights the need for care coordination, enhancement, and expansion of health care services after childbirth. Yet the prioritization of disease surveillance, management, and mitigation during birth and beyond within the American College of Obstetrics and Gynecology facilitates the medicalization and pathologization of Black bodies, voices, and power. Thus, we offer the Building and Bridging Black Futures Beyond Birth Model: A 12-Step Black Woman-Person First Approach, as a more humane and holistic model of culturally affirming and clinically responsive care. Destigmatizing and democratizing care bridges the gap between intent and impact in postpartum care optimization, particularly for Black women, girls, and gender expansive people and their communities.

Oxytocin and cardiometabolic interoception: Knowing oneself affects ingestive and social behaviors.

Maintaining homeostasis while navigating one's environment involves accurately assessing and interacting with external stimuli while remaining consciously in tune with internal signals such as hunger and thirst. Both atypical social interactions and unhealthy eating patterns emerge as a result of dysregulation in factors that mediate the prioritization and attention to salient stimuli. Oxytocin is an evolutionarily conserved peptide that regulates attention to exteroceptive and interoceptive stimuli in a social environment by functioning in the brain as a modulatory neuropeptide to control social behavior, but also in the periphery as a hormone acting at oxytocin receptors (Oxtr) expressed in the heart, gut, and peripheral ganglia. Specialized sensory afferent nerve endings of Oxtr-expressing nodose ganglia cells transmit cardiometabolic signals via the Vagus nerve to integrative regions in the brain that also express Oxtr(s). These brain regions are influenced by vagal sensory pathways and coordinate with external events such as those demanding attention to social stimuli, thus the sensations related to cardiometabolic function and social interactions are influenced by oxytocin signaling. This review investigates the literature supporting the idea that oxytocin mediates the interoception of cardiovascular and gastrointestinal systems, and that the modulation of this awareness likewise influences social cognition. These concepts are then considered in relation to Autism Spectrum Disorder, exploring how atypical social behavior is comorbid with cardiometabolic dysfunction.

A Novel Organ-Specific Approach to Selectively Target Sensory Afferents Innervating the Aortic Arch.

The brain maintains cardiovascular homeostasis, in part, via the arterial baroreflex which senses changes in blood pressure (BP) at the level of the aortic arch. Sensory afferents innervating the aortic arch employ baroreceptors to convert stretch exerted on the arterial wall into action potentials carried by the vagus nerve to second order neurons residing within the nucleus of the solitary tract (NTS). Although the baroreflex was described more than 80 years ago, the specific molecular, structural, and functional phenotype of the baroreceptors remain uncharacterized. This is due to the lack of tools that provide the genetic and target organ specificity that is required to selectively characterize baroreceptor afferents. Here, we use a novel approach to selectively target baroreceptors. Male mice on a C57BL/6J background were anesthetized with isoflurane, intubated, and artificially ventilated. Following sternotomy, the aortic arch was exposed, and a retrograde adeno-associated virus was applied to the aortic arch to direct the expression of channelrhoropsin-2 (ChR2) and/or tdTomato (tdTom) to sensory afferents presumably functioning as baroreceptors. Consistent with the structural characteristics of arterial baroreceptors, robust tdTom expression was observed in nerve endings surrounding the aortic arch, within the fibers of the aortic depressor and vagus nerves, cell bodies of the nodose ganglia (NDG), and neural projections to the caudal NTS (cNTS). Additionally, the tdTom labeled cell bodies within the NDG also expressed mRNAs coding for the mechanically gated ion channels, PIEZO-1 and PIEZO-2. In vitro electrophysiology revealed that pulses of blue light evoked excitatory post-synaptic currents in a subset of neurons within the cNTS, suggesting a functional connection between the labeled aortic arch sensory afferents and second order neurons. Finally, the in vivo optogenetic stimulation of the cell bodies of the baroreceptor expressing afferents in the NDG produced robust depressor responses. Together, these results establish a novel approach for selectively targeting sensory neurons innervating the aortic arch. This approach may be used to investigate arterial baroreceptors structurally and functionally, and to assess their role in the etiology or reversal of cardiovascular disease.

Psychometric validation of a patient-reported experience measure of obstetric racism© (The PREM-OB Scale™ suite).

BACKGROUND: Perinatal quality improvement lacks valid tools to measure adverse hospital experiences disproportionately impacting Black mothers and birthing people. Measuring and mitigating harm requires using a framework that centers the lived experiences of Black birthing people in evaluating inequitable care, namely, obstetric racism. We sought to develop a valid patient-reported experience measure (PREM) of Obstetric Racism© in hospital-based intrapartum care designed for, by, and with Black women as patient, community, and content experts. METHODS: PROMIS© instrument development standards adapted with cultural rigor methodology. Phase 1 included item pool generation, modified Delphi method, and cognitive interviews. Phase 2 evaluated the item pool using factor analysis and item response theory. RESULTS: Items were identified or written to cover 7 previously identified theoretical domains. 806 Black mothers and birthing people completed the pilot test. Factor analysis concluded a 3 factor structure with good fit indices (CFI = 0.931-0.977, RMSEA = 0.087-0.10, R2  > .3, residual correlation < 0.15). All items in each factor fit the IRT model and were able to be calibrated. Factor 1, "Humanity," had 31 items measuring experiences of safety and accountability, autonomy, communication, and empathy. A 12-item short form was created to ease respondent burden. Factor 2, "Racism," had 12 items measuring experiences of neglect and mistreatment. Factor 3, "Kinship," had 7 items measuring hospital denial and disruption of relationships between Black mothers and their child or support system. CONCLUSIONS: The PREM-OB Scale™ suite is a valid tool to characterize and quantify obstetric racism for use in perinatal improvement initiatives.

Risk of early birth by body mass index in a propensity score-matched sample: A retrospective cohort study.

OBJECTIVE: Evaluate the risk of preterm (<37 weeks) or early term birth (37 or 38 weeks) by body mass index (BMI) in a propensity score-matched sample. DESIGN: Retrospective cohort analysis. SETTING: California, USA. POPULATION: Singleton live births from 2011-2017. METHODS: Propensity scores were calculated for BMI groups using maternal factors. A referent sample of women with a BMI between 18.5 and <25.0 kg/m2 was selected using exact propensity score matching. Risk ratios for preterm and early term birth were calculated. MAIN OUTCOME MEASURES: Early birth. RESULTS: Women with a BMI <18.5 kg/m2 were at elevated risk of birth of 28-31 weeks (relative risk [RR] 1.2, 95% CI 1.1-1.4), 32-36 weeks (RR 1.3, 95% CI 1.2-1.3), and 37 or 38 weeks (RR 1.1, 95% CI 1.1-1.1). Women with BMI ≥25.0 kg/m2 were at 1.2-1.4-times higher risk of a birth <28 weeks and were at reduced risk of a birth between 32 and 36 weeks (RR 0.8-0.9) and birth during the 37th or 38th week (RR 0.9). CONCLUSION: Women with a BMI <18.5 kg/m2 were at elevated risk of a preterm or early term birth. Women with BMI ≥25.0 kg/m2 were at elevated risk of a birth <28 weeks. Propensity score-matched women with BMI ≥30.0 kg/m2 were at decreased risk of a spontaneous preterm birth with intact membranes between 32 and 36 weeks, supporting the complexity of BMI as a risk factor for preterm birth. TWEETABLE ABSTRACT: Propensity score-matched women with BMI ≥30 kg/m2 were at decreased risk of a late spontaneous preterm birth.

Targeting angiotensin type-2 receptors located on pressor neurons in the nucleus of the solitary tract to relieve hypertension in mice.

AIMS: These studies evaluate whether angiotensin type-2 receptors (AT2Rs) that are expressed on γ-aminobutyric acid (GABA) neurons in the nucleus of the solitary tract (NTS) represent a novel endogenous blood pressure-lowering mechanism. METHODS AND RESULTS: Experiments combined advanced genetic and neuroanatomical techniques, pharmacology, electrophysiology, and optogenetics in mice to define the structure and cardiovascular-related function of NTS neurons that contain AT2R. Using mice with Cre-recombinase directed to the AT2R gene, we discovered that optogenetic stimulation of AT2R-expressing neurons in the NTS increases GABA release and blood pressure. To evaluate the role of the receptor, per se, in cardiovascular regulation, we chronically delivered C21, a selective AT2R agonist, into the brains of normotensive mice and found that central AT2R activation reduces GABA-related gene expression and blunts the pressor responses induced by optogenetic excitation of NTS AT2R neurons. Next, using in situ hybridization, we found that the levels of Agtr2 mRNAs in GABAergic NTS neurons rise during experimentally induced hypertension, and we hypothesized that this increased expression may be exploited to ameliorate the disease. Consistent with this, final experiments revealed that central administration of C21 attenuates hypertension, an effect that is abolished in mice lacking AT2R in GABAergic NTS neurons. CONCLUSION: These studies unveil novel hindbrain circuits that maintain arterial blood pressure, and reveal a specific population of AT2R that can be engaged to alleviate hypertension. The implication is that these discrete receptors may serve as an access point for activating an endogenous depressor circuit.

Imprecision in Precision Medicine: Differential Response of a Disease-Linked GluN2A Mutant to NMDA Channel Blockers.

Mutations in N-methyl-d-aspartate receptors (NMDAR) subunits have been implicated in a growing number of human neurodevelopmental disorders. Previously, a de novo mutation in GRIN2A, encoding the GluN2A subunit, was identified in a patient with severe epilepsy and developmental delay. This missense mutation, which leads to GluN2A-P552R, produces significant dendrotoxicity in transfected rodent cortical neurons, as evidenced by pronounced dendritic blebbing. This injurious process can be prevented by treatment with the NMDA antagonist memantine. Given the increasing use of FDA approved NMDA antagonists to treat patients with GRIN mutations, who may have seizures refractory to traditional anti-epileptic drugs, we investigated whether additional NMDA antagonists were effective in attenuating neurotoxicity associated with GluN2A-P552R expression. Intriguingly, we found that while treatment with memantine can effectively block GluN2A-P552R-mediated dendrotoxicity, treatment with ketamine does not, despite the fact that both drugs work as open NMDAR channel blockers. Interestingly, we found that neurons expressing GluN2A-P552R were more vulnerable to an excitotoxic insult-an effect that, in this case, could be equally rescued by both memantine and ketamine. These findings suggest that GluN2A-P552R induced dendrotoxicity and increased vulnerability to excitotoxic stress are mediated through two distinct mechanisms. The differences between memantine and ketamine in halting GluN2A-P552R dendrotoxicity could not be explained by NMDA antagonist induced changes in MAP or Src kinase activation, previously shown to participate in NMDA-induced excitotoxicity. Our findings strongly suggest that not all NMDA antagonists may be of equal clinical utility in treating GRIN2A-mediated neurological disorders, despite a shared mechanism of action.

The association of COVID-19 infection in pregnancy with preterm birth: A retrospective cohort study in California.

INTRODUCTION: Our understanding of the association between coronavirus disease 19 (COVID-19) and preterm or early term birth among racially and ethnically diverse populations and people with chronic medical conditions is limited. METHODS: We determined the association between COVID-19 and preterm (PTB) birth among live births documented by California Vital Statistics birth certificates between July 2020 and January 2021 (n=240,147). We used best obstetric estimate of gestational age to classify births as very preterm (VPTB, <32 weeks), PTB (< 37 weeks), early term (37 and 38 weeks), and term (39-44 weeks), as each confer independent risks to infant health and development. Separately, we calculated the joint effects of COVID-19 diagnosis, hypertension, diabetes, and obesity on PTB and VPTB. FINDINGS: COVID-19 diagnoses on birth certificates increased for all racial/ethnic groups between July 2020 and January 2021 and were highest for American Indian/Alaska Native (12.9%), Native Hawaiian/Pacific Islander (11.4%), and Latinx (10.3%) birthing people. COVID-19 diagnosis was associated with an increased risk of VPTB (aRR 1.6, 95% CI [1.4, 1.9]), PTB (aRR 1.4, 95% CI [1.3, 1.4]), and early term birth (aRR 1.1, 95% CI [1.1, 1.2]). There was no effect modification of the overall association by race/ethnicity or insurance status. COVID-19 diagnosis was associated with elevated risk of PTB in people with hypertension, diabetes, and/or obesity. INTERPRETATION: In a large population-based study, COVID-19 diagnosis increased the risk of VPTB, PTB, and early term birth, particularly among people with medical comorbidities. Considering increased circulation of COVID-19 variants, preventative measures, including vaccination, should be prioritized for birthing persons. FUNDING: UCSF-Kaiser Department of Research Building Interdisciplinary Research Careers in Women's Health Program (BIRCWH) National Institute of Child Health and Human Development (NICHD) and the Office of Research on Women's Health (ORWH) [K12 HD052163] and the California Preterm Birth Initiative, funded by Marc and Lynn Benioff.

Pregnant people's experiences discussing their cannabis use with prenatal care providers in a state with legalized cannabis.

BACKGROUND: As cannabis legalization spreads, so do concerns about potential harms from use during pregnancy. Legalization may facilitate improved patient-provider interactions about cannabis use. Yet little is known about pregnant people's discussions of cannabis use with healthcare providers in an environment where recreational cannabis is legal. METHODS: In May-August 2019, we conducted semi-structured in-depth interviews with 33 pregnant or postpartum people in California who used cannabis during pregnancy, and explored their discussions with healthcare providers about their cannabis use. We audio-recorded and transcribed interviews, and conducted thematic analysis using inductive and deductive methods. RESULTS: Participants were diverse by age, race/ethnicity, and socio-economic position. Most reported daily cannabis use, both before and during pregnancy. Most participants did not disclose their cannabis use to their prenatal care providers, due to fears of being reported to child protective services (CPS), or fears of provider judgment. Participants reported that few providers initiated any discussions about cannabis use in pregnancy with them; some participants interpreted this omission as tacit endorsement of cannabis use in pregnancy. When participants and providers did discuss cannabis use in pregnancy, participants heard a wide range of sometimes-conflicting health messages, as well as some legal threats. CONCLUSIONS: This study documents notable deficits in patient-provider interactions about cannabis. Pregnant patients' fears of being reported to CPS and separated from their children for cannabis use persist despite cannabis legalization. Providers' role as potential reporters to CPS appears to pose a significant barrier to comprehensive, compassionate counseling and education on cannabis use in pregnancy.

Maternal nativity and risk of adverse perinatal outcomes among Black women residing in California, 2011-2017.

OBJECTIVE: Examine the risk of adverse perinatal outcomes among the United States (US)-born and foreign-born Black women in California. STUDY DESIGN: The study comprised all singleton live births to Black women in California between 2011 and 2017. We defined maternal nativity as US-born or foreign-born. Using Poisson regression, we computed risk ratios (RR) and 95% confidence intervals (CI) for three adverse perinatal outcomes: preterm birth, small for gestational age deliveries, and infant mortality. RESULTS: Rates of adverse perinatal outcomes were significantly higher among US-born Black women. In adjusted models, US-born Black women experienced an increased risk of preterm birth (RR 1.51, 95% CI 1.39, 1.65) and small for gestational age deliveries (RR 1.52, 95% CI 1.41, 1.64), compared to foreign-born Black women. CONCLUSIONS: Future studies should consider experiences of racism across the life course when exploring heterogeneity in the risk of adverse perinatal outcomes by nativity among Black women in the US.

Early-life oxytocin attenuates the social deficits induced by caesarean-section delivery in the mouse.

The oxytocin (OXT) system has been strongly implicated in the regulation of social behaviour and anxiety, potentially contributing to the aetiology of a wide range of neuropathologies. Birth by Caesarean-section (C-section) results in alterations in microbiota diversity in early-life, alterations in brain development and has recently been associated with long-term social and anxiety-like behaviour deficits. In this study, we assessed whether OXT intervention in the early postnatal period could reverse C-section-mediated effects on behaviour, and physiology in early life and adulthood. Following C-section or per vaginum birth, pups were administered with OXT (0.2 or 2 µg/20 µl; s.c.) or saline daily from postnatal days 1-5. We demonstrate that early postnatal OXT treatment has long-lasting effects reversing many of the effects of C-section on mouse behaviour and physiology. In early-life, high-dose OXT administration attenuated C-section-mediated maternal attachment impairments. In adulthood, low-dose OXT restored social memory deficits, some aspects of anxiety-like behaviour, and improved gastrointestinal transit. Furthermore, as a consequence of OXT intervention in early life, OXT plasma levels were increased in adulthood, and dysregulation of the immune response in C-section animals was attenuated by both doses of OXT treatment. These findings indicate that there is an early developmental window sensitive to manipulations of the OXT system that can prevent lifelong behavioural and physiological impairments associated with mode of birth.

Identification of Novel Cross-Talk between the Neuroendocrine and Autonomic Stress Axes Controlling Blood Pressure.

The hypothalamic paraventricular nucleus (PVN) controls neuroendocrine axes and the autonomic nervous system to mount responses that cope with the energetic burdens of psychological or physiological stress. Neurons in the PVN that express the angiotensin Type 1a receptor (PVNAgtr1a) are implicated in neuroendocrine and autonomic stress responses; however, the mechanism by which these neurons coordinate activation of neuroendocrine axes with sympathetic outflow remains unknown. Here, we use a multidisciplinary approach to investigate intra-PVN signaling mechanisms that couple the activity of neurons synthesizing corticotropin-releasing-hormone (CRH) to blood pressure. We used the Cre-Lox system in male mice with in vivo optogenetics and cardiovascular recordings to demonstrate that excitation of PVNAgtr1a promotes elevated blood pressure that is dependent on the sympathetic nervous system. Next, neuroanatomical experiments found that PVNAgtr1a synthesize CRH, and intriguingly, fibers originating from PVNAgtr1a make appositions onto neighboring neurons that send projections to the rostral ventrolateral medulla and express CRH type 1 receptor (CRHR1) mRNA. We then used an ex vivo preparation that combined optogenetics, patch-clamp electrophysiology, and Ca2+ imaging to discover that excitation of PVNAgtr1a drives the local, intra-PVN release of CRH, which activates rostral ventrolateral medulla-projecting neurons via stimulation of CRHR1(s). Finally, we returned to our in vivo preparation and found that CRH receptor antagonism specifically within the PVN lowered blood pressure basally and during optogenetic activation of PVNAgtr1a Collectively, these results demonstrate that angiotensin II acts on PVNAgtr1a to conjoin hypothalamic-pituitary-adrenal axis activity with sympathetically mediated vasoconstriction in male mice.SIGNIFICANCE STATEMENT The survival of an organism is dependent on meeting the energetic demands imposed by stressors. This critical function is accomplished by the CNS's ability to orchestrate simultaneous activities of neurosecretory and autonomic axes. Here, we unveil a novel signaling mechanism within the paraventricular nucleus of the hypothalamus that links excitation of neurons producing corticotropin-releasing-hormone with excitation of neurons controlling sympathetic nervous system activity and blood pressure. The implication is that chronic stress exposure may promote cardiometabolic disease by dysregulating the interneuronal cross-talk revealed by our experiments.

Black Women's Perspectives on Structural Racism across the Reproductive Lifespan: A Conceptual Framework for Measurement Development.

BACKGROUND: Exposures to structural racism has been identified as one of the leading risk factors for adverse maternal and infant health outcomes among Black women; yet current measures of structural racism do not fully account for inequities seen in adverse maternal and infant health outcomes between Black and white women and infants. In response, the purpose of this study was to conceptualize structural racism from the perspectives of Black women across the reproductive lifespan and its potential impact on adverse maternal and infant health outcomes. METHODS: We conducted a series of focus groups with 32 Black women across the reproductive lifespan (5 preconception, 13 pregnant, and 14 postpartum). Study criteria including self-identifying as Black, residing in Oakland or Fresno, California and representing one of three reproductive life tracks (preconception, pregnant, postpartum). We consulted with study participants and an expert advisory board to validate emergent domains of structural racism. RESULTS: Nine domains of structural racism emerged from a ground theory constant comparative analysis: Negative Societal Views; Housing; Medical Care; Law Enforcement; Hidden Resources; Employment; Education, Community Infrastructure; and Policing Black Families. CONCLUSIONS FOR PRACTICE: Findings from this study suggest that there is an interplay among structural racism, and social and structural determinants of health which has negative impacts on Black women's sexual and reproductive health. Furthermore, findings from this study can be used to develop more comprehensive medical assessments and policies to address structural racism experienced by Black women across the reproductive lifespan.

Racial and Ethnic Disparities in Hospital-Based Care Associated with Postpartum Depression.

OBJECTIVE: To estimate racial and ethnic differences in rates of hospital-based care associated with postpartum depression. METHODS: This is a retrospective cohort study using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes within data from the Office of Statewide Planning and Development in California. We included primiparous women who underwent delivery hospitalization from 2008 to 2012. The primary outcome was the first postpartum hospital encounter with a ICD-9-CM code for depression over a 9-month period after delivery. We examined the cumulative incidence of hospital-based care for postpartum depression by race/ethnicity. Logistic regression was used to estimate relative risk. RESULTS: The study cohort consisted of 984,167 primiparous women: 314,037 (32%) were non-Hispanic White; 59,754 (6%) were non-Hispanic Black; 150,855 (15%) were non-Hispanic Asian; 448,770 (46%) were Hispanic; and 10,399 (1%) were other races. The cumulative incidence of hospital-based care for postpartum depression was highest for Black women (39; 95% CI = 34-44 per 10,000 deliveries) and lowest for Asian women (7; 95% CI = 5-8 per 10,000 deliveries). Compared with White women, hospital-based care for postpartum depression was more likely to be provided to Black women (OR = 2.3; 95% CI = 1.9-2.7), whereas care was less likely for Asians (OR = 0.4; 95% CI = 0.3-0.5) and Hispanics (OR = 0.8; 95% CI = 0.7-1.0). Similar findings were observed after excluding women with antepartum depression, adjusting for sociodemographic and clinical variables, and stratifying according to care settings. CONCLUSION: Compared with White women, hospital-based care for postpartum depression more frequently impacts Black women. Identifying and improving inequities in access to and utilization of mental health care for postpartum women should be a maternal health priority.