Accelerated age-related decline in renal and vascular function in female rats following early-life growth restriction.

Many studies report sexual dimorphism in the fetal programming of adult disease. We hypothesized that there would be differences in the age-related decline in renal function between male and female intrauterine growth-restricted rats. Early-life growth restriction was induced in rat offspring by administering a low-protein diet (LPD; 8.7% casein) to dams during pregnancy and lactation. Control dams were fed a normal-protein diet (NPD; 20% casein). Mean arterial pressure (MAP) and renal structure and function were assessed in 32- and 100-wk-old offspring. Mesenteric artery function was examined at 100 wk using myography. At 3 days of age, body weight was ∼24% lower (P < 0.0001) in LPD offspring; this difference was still apparent at 32 wk but not at 100 wk of age. MAP was not different between the male NPD and LPD groups at either age. However, MAP was greater in LPD females compared with NPD females at 100 wk of age (∼10 mmHg; P < 0.001). Glomerular filtration rate declined with age in the NPD male, LPD male and LPD female offspring (∼45%, all P < 0.05), but not in NPD female offspring. Mesenteric arteries in the aged LPD females had reduced sensitivity to nitric oxide donors compared with their NPD counterparts, suggesting that vascular dysfunction may contribute to the increased risk of disease in aged females. In conclusion, females growth-restricted in early life were no longer protected from an age-related decline in renal and arterial function, and this was associated with increased arterial pressure without evidence of renal structural damage.

Antecedents and consequences of workplace aggression in the allied health context.

Workplace aggression research has typically focused on groups in the health care industry considered to be high risk (e.g., nursing); however, aggression also occurs among other health care professional groups, such as those in allied health. This study aimed to investigate the antecedents and consequences of workplace aggression among allied health professionals. Allied health professionals working for an Australian health care organization were surveyed, with 134 (49%) responding. The largest group of allied health professionals surveyed were social workers (49%). Job demands, job control, and social support were linked to different types of aggression. Different sources of aggression were linked to various employee outcomes. The importance of considering stressors surrounding employee work conditions is highlighted.

How can psychologists meet the needs of autistic adults?

LAY ABSTRACT: In a recent editorial, Mandy described an autism mental health crisis because autistic people are more likely to experience mental health concerns, yet they are less likely to get help. When autistic people do seek support, services tend not to be well matched to their needs. Alongside the six ideas Mandy suggested for addressing the mental health crisis, we think it is essential for psychologists to start changing the way they work to improve the person-environment fit for autistic clients. The relationship between a psychologist and their client influences the gains a client makes from engaging in therapy. The way psychologists are trained to build an effective working relationship with clients is based on neurotypical communication styles. The double empathy problem tells us that autistic clients relate to others differently to non-autistic clients, and so we propose that psychologists, especially when not autistic themselves, need to build the therapeutic relationship in a different way. We feel this is important, as the relationship between a psychologist and client is understood to be an important factor in how much the client can benefit from therapy. In this letter, we draw upon Bulluss' call for cultural competency when working with autistic clients, and further insights from autistic psychologists, and propose that psychologists rethink some taken-for-granted aspects of practice to be better able to create a sense of interpersonal safety when working with autistic clients.

"Maybe No One Knows We Need Help": Understanding the Experiences of Autistic Working Mothers in Australia.

Background: Although there are no known studies investigating autistic working mothers, research has demonstrated that managing employment and motherhood in non-autistic populations has specific challenges, as does employment in autistic populations. This autistic-led study aimed at investigating the experience of autistic working mothers to identify benefits, challenges, and support needs. Methods: We utilized a subjectivist epistemological perspective to learn about the experiences of autistic working mothers. We recruited 10 autistic working mothers (aged 34-50 years) via social media advertisements, who participated in a 45- to 60-minute semi-structured interview where we asked questions developed in consultation with a community reference group. We transcribed interviews and then analyzed them using inductive reflexive thematic analysis. Results: We identified three key themes. The first theme, "Wellbeing: Work gives me purpose," discusses how employment supports mental well-being. The second theme, "Challenges: It's hard being an autistic working mother," includes the challenges of balancing work and caregiving, guilt related to being a working mother, and issues with part-time work. The third theme, "The invisible disability: Everyone thinks I look okay," discusses the lack of understanding of participants' challenges, with assumptions they are coping, and the lack of supports that led to some participants no longer seeking assistance. Conclusions: The responses of the autistic women who took part support a view that autistic working mothers may experience some similar challenges to non-autistic working mothers, including stress in juggling caring and work roles. They identified additional challenges related to their gender and their autistic identity, including a lack of understanding of the female (or "internalized") presentation of autism. These findings will help autistic working mothers by promoting a better understanding of their experiences and challenges when they speak with health professionals, government, and employers seeking support and accommodations.

Why is this an important issue?: We did not find any existing research about the experiences of autistic women who are working mothers. However, we felt this was an important topic to investigate because previous research involving women who are not autistic has reported that being a working mother can be challenging. In addition, previous autism research has found that autistic people can find aspects of work difficult. What was the purpose of this study?: We wanted to find out about the experiences of autistic working mothers and their support needs. What did the researchers do?: We recruited 10 autistic working mothers (aged 34­50 years), through social media advertisements. We interviewed each participant separately and the interviews took between 45 and 60 minutes. We asked each participant the same set of questions to understand their perspectives on the benefits and challenges of being a mother, an employee, and a working mother, and to find out where they needed support. We then analyzed the interview transcripts to find common themes. What were the results of the study?: We identified three key themes about the experience of autistic working mothers. The first theme called "Wellbeing: Work gives me purpose" discusses how employment supports mental well-being and financial independence. The second theme, "Challenges: It's hard being an autistic working mother," includes the challenges in balancing work and caregiving, guilt related to being a working mother, and issues with part-time work. The third theme called "The invisible disability: Everyone thinks I look okay" discusses a lack of understanding of participants' challenges, with assumptions they are coping, and the lack of supports for autistic working mothers that led to some participants no longer seeking assistance. What do these findings add to what was already known?: We found that autistic working mothers may experience some challenges, which are similar to those identified in previous studies involving working mothers who are not autistic such as stress related to juggling being a mother and an employee. In addition to this, they may experience other challenges related to their gender and their autism, such as a lack of understanding of how autistic women mask and camouflage and assumptions by professionals that autistic working mothers are coping because they previously managed employment and parenting without any support. What are the potential weaknesses in the study?: One limitation of our study is that the participant group lacks diversity. For example, it does not include autistic people from a range of cultural backgrounds such as First Nations Australians, or from a range of educational and socio-economic backgrounds. Although the study was open to participants who identify their gender as non-binary, no non-binary autistic people registered for the study. This meant our results only included the views of autistic working mothers who identify as women and have completed further education after high school. In addition, 90% of participants were diagnosed with autism as adults. Although late diagnosis is common, especially in women, it may also mean that some of the results were specific to this group. Future research could address these issues by having a larger participant group, which specifically includes those from diverse cultural, educational, and socioeconomic backgrounds, gender diverse participants, and both early- and late-diagnosed autistic women and non-binary people. How will these findings help autistic adults now or in the future?: These findings will help autistic working mothers by promoting a better understanding of their experiences and challenges when they speak with health professionals, government, and employers seeking support and accommodations.

An ecological systems model of employee experience in industry-led autism employment programmes.

LAY ABSTRACT: We asked 33 autistic adults from two industry-led employment programmes about their experiences in the programmes. These are programmes started by companies to recruit and support autistic people in work. We also asked about their workplace supports, relationships and how they thought the programme had impacted their life. Understanding the experiences of people in these industry-led employment programmes is important as the information can help to improve the programmes and participants' experiences. After reviewing the interviews, we found five themes that best described the employee's experience: (1) working involves multiple job tasks that evolve as the employment context changes; (2) relationships in the workplace are diverse and are influenced by the type of work participants do and the work environment; (3) workplace needs change as the autistic employees learn to navigate their work environment; (4) autistic employees develop a professional identity in the workplace as they master work and feel more integrated in the workplace; and (5) recommendations for the development of supportive workplace environments for autistic people. We explored the way that aspects of the two employment programmes (e.g. training) and factors outside the programme changed with time and contributed to the participant's experience. We developed a new model to capture individual and workplace factors that contribute to the experience of autistic people who participate in industry employment programmes.

The oppressive nature of work in healthcare: predictors of aggression against nurses and administrative staff.

AIMS: To assess the antecedents of workplace aggression (bullying and violence) among nurses and administration staff. BACKGROUND: As a result of power structures within the healthcare industry, nurses and administration staff may be more vulnerable to workplace aggression. Environmental and individual characteristics have been linked to the occurrence of such aggression among other groups. However, most research focuses on bullying, rarely extending these ideas to violence or nurses and administration staff specifically. METHODS: Surveys were distributed to nurses and administration staff employed by an Australian healthcare organisation. Aggression types (bullying and violence), as well as environmental (demands, control and support) and individual (negative affectivity, NA) characteristics were measured. RESULTS: External emotional abuse was most frequently reported for nurses (29%) and bullying for administration staff (27%). Demands, support and NA were associated with different aggression types in nurses, whereas for administration staff, control, support and NA were linked. CONCLUSION(S): Low support and high NA are particularly important to nurses and administration staff and their experiences of aggression. IMPLICATIONS FOR NURSING MANAGEMENT: Appropriate training for managers in providing support and acknowledging individual factors associated with aggression is essential. Further, managers should monitor aggression risk from patients and their associations towards staff in busy times.

Women seeking an autism diagnosis in Australia: A qualitative exploration of factors that help and hinder.

LAY ABSTRACT: An autism diagnosis can have a big impact on women and make it possible to access support. This study explored women's experiences of being diagnosed with autism as an adult in Australia, to try to understand what was helpful (facilitators) and unhelpful (barriers) for them during this process. We interviewed 10 autistic women who had been diagnosed in the last 5 years. Framework analysis was used to understand the data. We wanted to understand barriers and facilitators relating to the individual participants, the professionals they saw and the system they went through for their diagnostic assessment. Women reported that being able to recognise they were autistic, being motivated, preparing for the assessment, having social support and unmasking to be themselves were helpful during the diagnostic process. They reported that having a knowledgeable diagnostician who made accommodations for their needs assisted them during the assessment process. When providers dismissed the participants when they first raised the possibility they were autistic, it delayed them in seeking an assessment. At the system level, the women in this study found some aspects of the healthcare system difficult to navigate, particularly costs and long waitlists. Some found the assessment tools used were not well suited to them. The experiences of the women in this study highlight improvements that could be made to accessing an adulthood autism diagnosis in Australia. These include improving provider knowledge of the varied presentation of autism and the development of resources to help autistic women prepare for their diagnostic assessment.

'If I'm just me, I doubt I'd get the job': A qualitative exploration of autistic people's experiences in job interviews.

LAY ABSTRACT: When applying for a job, autistic job candidates are likely to face a number of challenges. Job interviews are one of these challenges - they require communicating and relationship-building with unfamiliar people and involve expectations about behaviour (that may vary between companies and are not made clear to job candidates). Given autistic people communicate differently to non-autistic people, autistic job candidates may be disadvantaged in the interview process. Autistic candidates may not feel comfortable or safe sharing with organisations their autistic identity and may feel pressure to hide any characteristics or behaviour they feel might indicate they are autistic. To explore this issue, we interviewed 10 autistic adults about their job interview experiences in Australia. We analysed the content of the interviews and found three themes that related to the individual person and three themes that related to environmental factors. Participants told us that they engaged in camouflaging behaviour during job interviews, feeling pressure to conceal aspects of themselves. Those who camouflaged during job interviews reported that it took a lot of effort, which resulted in increased stress, anxiety and exhaustion. The autistic adults we spoke to reported a need for inclusive, understanding and accommodating employers to help them feel more comfortable disclosing their autism diagnosis in the job application process. These findings add to current research that has explored camouflaging behaviour and barriers to employment for autistic people.

The Efficacy of Disability Employment Service (DES) Providers Working with Autistic Clients.

The efficacy of the Australian Disability Employment Services (DES) for autistic jobseekers has not been examined and is currently undergoing Government reform. To help inform the new DES strategy, we sought the views of: 24 autistic individuals; seven family members of autistic individuals, and; 46 DES employees. Data were collected using surveys and interviews. Data were analysed using Mann Whitney tests plus deductive thematic analysis based on Nicholas and colleagues' ecosystems model. Participants highlighted a need to adapt existing policies to enhance flexibility of the DES model. There was participant consensus that DES staff require specific education and training to meet the needs of autistic people. Suggestions to inform the new model of DES for autistic people are made.

Barriers to Employment: Raters' Perceptions of Male Autistic and Non-Autistic Candidates During a Simulated Job Interview and the Impact of Diagnostic Disclosure.

Background: Autistic individuals face low rates of engagement in the labor force. There is evidence that job interviews pose a significant barrier to autistic people entering the workforce. In this experimental study, we investigated the impact of diagnostic disclosure on decisions concerning candidate suitability during job interviews. Methods: Participants (n = 357; 59% female) from the general population rated 10 second "thin slices" of simulated job interviews of one male autistic and one male non-autistic candidate. In a between-subjects design, autism diagnostic disclosure was manipulated (None, Brief, and Detailed), so that neither ("None" condition) or both ("Brief" and "Detailed" conditions) candidates were labeled as autistic before the simulated interview (with additional information provided about autism in the "Detailed" condition). Results: Results for 255 non-autistic raters (57.6% female) were analyzed. Participants gave more favorable ratings of first impressions, employability, and endorsement for candidates labeled as autistic, irrespective of the actual diagnostic status (i.e., autistic and non-autistic) of the individual. Participants rated non-autistic candidates more favorably on all employment measures (first impressions, employability, and endorsement), and "hired" non-autistic candidates more frequently, compared with autistic candidates. Providing additional information about autism did not result in improved ratings. However, the discrepancy between autistic and non-autistic people chosen for "hire" was reduced when more information was provided. Conclusions: Although we found some support for the benefits of diagnostic disclosure during a simulated interview, these benefits were not restricted to autistic candidates and may be a positive bias associated with the diagnostic label. Contrary to our predictions, providing information about autism in addition to the diagnostic label did not have an overall impact on results. More research is required to determine whether benefits outweigh any risks of disclosure for autistic job candidates, and whether training interviewers about autism might improve employment outcomes for autistic job seekers. Lay summary: Why was this study done?: Job interviews seem to be a barrier to employment for autistic people. This is problematic, as job interviews are typically a part of the job application process.What was the purpose of this study?: We wanted to explore how non-autistic people perceive male autistic job candidates, and how this compares with male non-autistic candidates. We also wanted investigate whether disclosing that the candidate was autistic changed the raters' judgments of candidates, and if these judgments improved if more information about autism and employment was provided.What did the researchers do?: We showed 357 non-autistic participants short video snippets (∼10 seconds) of two "job candidates" (people who had completed a simulated job interview). Each participant was shown one video of an autistic job candidate, and one video of a non-autistic job candidate. Participants rated the candidates on two scales (employability and first impressions). After watching both videos, they chose which of the two candidates they would "hire" and gave an endorsement rating for each.Participants were in one of three conditions. Participants in the first condition ("None") were not given information about autism before watching the two videos. Participants in the second condition ("Brief") were told that both of the candidates were autistic. Participants in the third condition ("Detailed") were told that both candidates were autistic and were also provided with information about autism and the workplace. We told raters in the Brief and Detailed conditions that both the autistic and non-autistic candidate were autistic to explore if the diagnostic label influenced raters' perceptions of candidates separately to the actual diagnostic status of candidates.What were the results of the study?: Overall, the participants rated non-autistic candidates more favorably compared with autistic candidates. Participants gave more favorable job interview ratings for candidates when they were labeled as autistic, showing the autism label made a difference to how raters perceived candidates. Participants given information about autism and employment did not rate the candidates any higher than those in other two conditions, but they did "hire" more autistic candidates than the other participants.What do these findings add to what was already known?: The findings of this study provide some support that diagnostic disclosure may improve perceptions of autistic candidates (by non-autistic people) at job interview. Providing information about autism and the workplace in addition to disclosure may also provide some benefit, but more data are needed.What are potential weaknesses in the study?: Our findings may not reflect real-world settings. Further studies are also needed that include people of other genders. Given the small number of stimuli videos, and the many differences between autistic people, the less favorable ratings of autistic people should be interpreted with caution.How will these findings help autistic adults now or in the future?: The results of this study provide some evidence that there may be some benefit of disclosing an autism diagnosis during a job interview to non-autistic people. However, diagnostic disclosure is a complex and personal choice.

Brief Report: What Happens After School? Exploring Post-school Outcomes for a Group of Autistic and Non-autistic Australian Youth.

Young autistic Australians are less likely to attend higher education and have lower employment rates than non-autistic Australians (in: Australian Bureau of Statistics, Survey of disability, ageing and carers Australia: Summary of Findings 2018. Australian Bureau of Statistics, Canberra, 2019a). Few studies have examined post-school outcomes among this population. Using data from the first phase of a national longitudinal study including autistic (n = 79) and non-autistic (n = 107) 17-25-year olds, we found young autistic adults were (a) less likely to be employed, (b) more likely to attend technical and further education (TAFE) than university, (c) more likely to enrol in higher education on a part-time basis and (d) less likely to be engaged in both higher education and employment, than their non-autistic peers. Findings highlight a need to understand post-school trajectories of young autistic adults.

Workplace Social Challenges Experienced by Employees on the Autism Spectrum: An International Exploratory Study Examining Employee and Supervisor Perspectives.

Social challenges represent a significantly under-researched area when it comes to the poor employment outcomes in autism. In this exploratory study employees on the autism spectrum (N = 29) and supervisors (N = 15), representing seven continents, provided 128 written examples of workplace-based social challenges, their interpretation, consequences and resolution. Content analysis revealed that types of social challenges were individually oriented or associated with the work-environment. Social challenges were frequently attributed to internal or personal factors with direct consequences for the employee. Resolutions were more frequently targeted toward the individual than the workplace, and hindered employees' experience of work. This international study represents a first look at the types of social challenges that impact equitable work participation of autistic people.

Chronic maternal hypertension characterized by renal dysfunction is associated with reduced placental blood flow during late gestation in rabbits.

Maternal hypertension associated with renal disease is a common pregnancy complication. Previously, we have shown in a rabbit model of mild hypertension that offspring from hypertensive mothers have increased blood pressure as adults. In human pregnancy, hypertension has been associated with decreased utero-placental blood flow. The aim of this study was to determine placental blood flow (PBF) in mild (2-kidney-1-wrapped; 2K-1W) and moderate (2-kidney-2-wrapped; 2K-2W) rabbit models of maternal hypertension. We hypothesized that PBF would be inversely related to the severity of the hypertension. PBF and renal blood flow (RBF) were measured using microspheres on day 28 of a 32-day gestation, in normotensive (sham), 2K-1W, and 2K-2W hypertensive groups. Mean arterial pressure (MAP, approximately 7 mmHg, P < 0.05) was increased, and RBF ( approximately 35%, P < 0.05) was reduced in the 2K-1W and 2K-2W (MAP approximately 20 mmHg, P < 0.01; RBF approximately 53%, P < 0.05) groups compared with the sham group. In the 2K-1W group, PBF fell by approximately 12% (P = 0.08) and fetal-to-placental weight ratio increased by approximately 12% (P < 0.01) compared with the sham group, reflecting an increase in the functional capacity of the placenta to deliver nutrients to the fetus. In the 2K-2W group, PBF decreased approximately 51% (P < 0.05) compared with the sham group, without changes in placental efficiency. Thus, in late gestation, placental blood flow was significantly reduced in the moderate hypertension group, without accompanying changes in fetal or placental weight or placental efficiency. In contrast, mild hypertension resulted in an increase in placental efficiency, without significant changes in placental blood flow. These findings suggest that mild and moderate hypertension may alter placental delivery of nutrients via differing mechanisms dependent upon the severity of the hypertension.

Fetal growth and well-being in a study of maternal hypertension in rabbits.

Obtaining growth and physiologic data in the postnatal laboratory animal is common. However, monitoring growth in utero is far more difficult, with little data available except upon termination of pregnancy. High-resolution ultrasound was used to monitor growth, morphology, and fetal well-being in normotensive and hypertensive rabbits (21 fetuses) at day 16, 20, and 26 of the 32 day gestational period. Set protocols, comparable to those routinely assessed in humans, were devised and followed for each examination. Birth weight was greater in offspring of hypertensive as compared to normotensive mothers (p < 0.001); however, litter size was reduced. The greater birth weight was reflected in growth parameters measured throughout gestation indicating the predictive value of ultrasound. High-resolution ultrasound was a reliable and sensitive method for biometric and morphologic assessment of the fetal rabbit, demonstrating that growth trajectory of offspring of hypertensive mothers may be altered early in gestation.

Cross-sectional and longitudinal predictors of quality of life in autistic individuals from adolescence to adulthood: The role of mental health and sleep quality.

LAY ABSTRACT: Research shows that autistic adults are at risk of a range of physical (e.g. sleep difficulties) and mental health (e.g. anxiety) conditions, as well as lower employment and post-secondary education participation; these all can affect one's quality of life. However, we have little information about what affects quality of life for autistic individuals across the lifespan and whether this differs from non-autistic people. We determined what factors (e.g. mental or physical health challenges) affected quality of life in a large group of autistic individuals aged 15-80 years compared with similar age non-autistic individuals. We also examined what factors affected quality of life of the autistic group 2 years later. We found a similar pattern of results for the autistic and non-autistic groups; depression symptoms, psychological well-being, sleep quality and autonomic symptoms (e.g. sweating) were all significant predictors of quality of life. In addition, among the autistic group, baseline quality of life had the most influence on quality of life 2 years later. These results have implications for support services, as they highlight the relationship between mental health (especially depression) and quality of life. Given that sleep challenges (e.g. insomnia) are related to mental health, an intervention addressing both insomnia and mental health may be most useful in helping autistic individuals improve their quality of life.

Chronic maternal hypertension affects placental gene expression and differentiation in rabbits.

BACKGROUND: Previously, we have shown that adult offspring from hypertensive rabbits develop hypertension. METHOD: We aimed to determine the effects of mild (+15 mmHg) and moderate (+25 mmHg) increases in maternal blood pressure and plasma renin activity on placental differentiation and expression of components of the renin-angiotensin system and 11[beta]-hydroxysteroid dehydrogenase type 2 mRNA in rabbits. Placentas were collected from normotensive (sham), mild (2-kidney-1-cellophane wrapped; 2K-1W) and moderate (2-kidney-2-cellophane wrapped; 2K-2W) hypertensive groups at gestational age of 14, 21 and 28 days. Placental gene expression was quantified by reverse transcriptase-PCR, and morphometry was assessed by videoimage analyses of placental sections. RESULTS: Fetal weight was similar between groups across gestation. In the 2K-1W group at gestational age day 14, fetal-to-placental weight ratio was increased (approximately 34%) as were volumes of fetal capillaries ([up arrow]56%) and maternal blood space at gestational age day 21 ([up arrow]55%) compared with sham (all P < 0.05). In the 2K-2W group, fetal-to-placental weight ratio was increased at gestational age day 21 (approximately 25%; P < 0.01) with an accompanying reduction in placental weight, and at gestational age day 28, volume density of fetal capillaries was increased (approximately 22%; P < 0.05). Placental renin mRNA was lower in both the 2K-1W (approximately 88%) and 2K-2W (approximately 98%) groups at gestational age day 28 (all P < 0.01). Placental 11[beta]-hydroxysteroid dehydrogenase type 2 mRNA was lower in the 2K-1W (approximately 36%) and 2K-2W (approximately 31%) groups at gestational age day 14 and greater (approximately 36%) in the 2K-2W group at gestational age day 21 (all P < 0.01). Associations between placental AT1R and AT2R mRNA and placental differentiation were disturbed by hypertension. CONCLUSION: Mild and moderate maternal hypertension differentially alters placental structure and gene expression that may affect placental functional capacity and contribute to programming of hypertension in offspring.

Enhanced angiotensin II type 2 receptor mechanisms mediate decreases in arterial pressure attributable to chronic low-dose angiotensin II in female rats.

The renin-angiotensin system is a far more complex enzymatic cascade than realized previously. Mounting evidence suggests sex-specific differences in the regulation of the renin-angiotensin system and arterial pressure. We examined the hemodynamic responses, angiotensin II receptor subtypes, and angiotensin-converting enzyme 2 gene expression levels after graded doses of angiotensin II in males and females. Mean arterial pressure was measured via telemetry in male and female rats in response to a 2-week infusion of vehicle, low-dose (50 ng/kg per minute SC) or high-dose (400 ng/kg per minute SC) angiotensin II. The effect of concurrent infusion of the angiotensin II type 2 receptor (AT(2)R) blocker (PD123319) was also examined. The arterial pressure response to high-dose angiotensin II was attenuated in females compared with males (24+/-8 mm Hg versus 42+/-5 mm Hg; P for the interaction between sex and treatment <0.002). Remarkably, low-dose angiotensin II decreased arterial pressure (11+/-4 mm Hg; P for the interaction between sex and treatment <0.02) at a dose that did not have an effect in males. This decrease in arterial pressure in females was abolished by AT(2)R blockade. Renal AT(2)R, angiotensin-converting enzyme 2, and left ventricular AT(2)R mRNA gene expressions were markedly greater in females than in males with a renal angiotensin II type 1a receptor:AT(2)R ratio of approximately 1 in females. Angiotensin II infusion did not affect renal AT(2)R mRNA expression but resulted in significantly less left ventricular mRNA expression. Renal angiotensin-converting enzyme 2 mRNA expression levels were greater in females than in males treated with high-dose angiotensin II (approximately 2.5 fold; P for the interaction between sex and treatment <0.05). In females, enhancement of the vasodilatory arm of the renin-angiotensin system, in particular, AT(2)R and angiotensin-converting enzyme 2 mRNA expression, may contribute to the sex-specific differences in response to renin-angiotensin system activation.

Effect of endothelin-1 on regional kidney blood flow and renal arteriole calibre in rabbits.

1. Medullary blood flow (MBF) is important in the long-term control of arterial pressure. However, it is unclear which vascular elements regulate MBF. 2. Exogenous endothelin (ET)-1 decreases cortical more than medullary blood flow. We hypothesized that ET-1 would therefore constrict afferent (AA) and efferent arterioles (EA) of juxtamedullary glomeruli less than those of cortical glomeruli. 3. Mean arterial pressure, renal blood flow and cortical (CBF) and medullary (MBF) blood flow, via laser-Doppler flowmetry, were measured before and after intrarenal ET-1 (2 ng/kg per min; n = 6) or vehicle (n = 6) in anaesthetized rabbits. Kidneys were perfusion fixed, vascular casts formed, lumen diameters measured via scanning electron microscopy and relative resistance calculated. 4. Mean arterial pressure was not significantly affected by ET-1 infusion. Cortical glomerular arteriole lumen diameters were significantly reduced in the ET-1-infused group (AA approximately 30%, EA approximately 18%; PA < 0.01), compatible with the decrease in CBF (42 +/- 3%; PGT < 0.01). Juxtamedullary arteriole lumen diameters were also significantly reduced in the ET-1-infused group (AA approximately 34%, EA approximately 21%; PA < 0.01); however, MBF did not decrease. 5. In conclusion, our data suggest that juxtamedullary arterioles are not of primary importance in the regulation of MBF because, despite reductions in juxtamedullary arteriole diameters in response to ET-1, MBF was not decreased.

Predominant postglomerular vascular resistance response to reflex renal sympathetic nerve activation during ANG II clamp in rabbits.

We have shown previously that a moderate reflex increase in renal sympathetic nerve activity (RSNA) elevated glomerular capillary pressure, whereas a more severe increase in RSNA decreased glomerular capillary pressure. This suggested that the nerves innervating the glomerular afferent and efferent arterioles could be selectively activated, allowing differential control of glomerular capillary pressure. A caveat to this conclusion was that intrarenal actions of neurally stimulated ANG II might have contributed to the increase in postglomerular resistance. This has now been investigated. Anesthetized rabbits were prepared for renal micropuncture and RSNA recording. One group (ANG II clamp) received an infusion of an angiotensin-converting enzyme inhibitor (enalaprilat, 2 mg/kg bolus plus 2 mg.kg(-1).h(-1)) plus ANG II ( approximately 20 ng.kg(-1).min(-1)), the other vehicle. Measurements were made before (room air) and during 14% O(2). Renal blood flow decreased less during ANG II clamp compared with vehicle [9 +/- 1% vs. 20 +/- 4%, interaction term (P(GT)) < 0.05], despite a similar increase in RSNA in response to 14% O(2) in the two groups. Arterial pressure and glomerular filtration rate were unaffected by 14% O(2) in both groups. Glomerular capillary pressure increased from 33 +/- 1 to 37 +/- 1 mmHg during ANG II clamp and from 33 +/- 2 to 35 +/- 1 mmHg in the vehicle group before and during 14% O(2), respectively (P(GT) < 0.05). During ANG II clamp, postglomerular vascular resistance was still increased in response to RSNA during 14% O(2), demonstrating that the action of the renal nerves on the postglomerular vasculature was independent of the renin-angiotensin system. This further supports our hypothesis that increases in RSNA can selectively control pre- and postglomerular vascular resistance and therefore glomerular ultrafiltration.