Health and economic burden of low back pain and rheumatoid arthritis attributable to smoking in 192 countries and territories in 2019.

BACKGROUND AND AIMS: Smoking is a risk factor for low back pain (LBP) and rheumatoid arthritis (RA). We aimed to estimate the global health and economic burden of LBP and RA attributable to smoking. DESIGN: This was a cross-sectional study. SETTING: The study was conducted in 192 countries and territories. CASES: Prevalent cases of LBP and RA were used, extracted from the Global Burden of Diseases, Injuries and Risk Factors Study 2019 data repositories. MEASUREMENTS: Smoking-attributable health and economic burden was estimated with the population-attributable fraction method. Smoking-attributable prevalence of LBP and RA and health-care costs were estimated for patients of all ages, whereas years lived with disability (YLDs) and productivity losses due to morbidity were estimated for patients aged 15-84 years. Uncertainty intervals (UIs) of the results were obtained by repeating the analysis with the lower and upper bounds of all input variables. FINDINGS: Globally, smoking accounted for 84.5 million (UI = 56.7-120.2 million) prevalent cases of LBP, 1.8 million (UI = 0.5-3.4 million) prevalent cases of RA and 11.3 million (UI = 6.2-18.5 million) YLDs, which represented 1.5% of all-cause YLDs in the working-age population aged 15-84 years in 2019. Health-care costs and productivity losses of smoking-attributable LBP and RA cost the global economy purchasing-power parity $326.0 billion (UI = $184.0-521.4 billion), representing 0.2% of the global gross domestic product. Specifically, smoking accounted for $65.8 billion (UI = $38.0-101.2 billion) in health-care costs world-wide, with more than half [$39.8 billion (UI = $23.1-61.3 billion), 60.6%] borne by the public sector. Smoking also contributed to $260.3 billion (UI = $146.0-420.3 billion) in productivity losses globally. Approximately 60.0% of the global YLDs were observed in middle-income countries, whereas 84.4% of health-care costs and 72.7% of productivity losses were borne by high-income countries. CONCLUSIONS: Globally, in 2019, smoking accounted for more than 11.0 million years lived with disability and purchasing-power parity $326.0 billion in economic losses due to low back pain and rheumatoid arthritis. Middle-income countries suffered more morbidity, whereas high-income countries experienced larger economic losses.

The global health and economic impact of low-back pain attributable to occupational ergonomic factors in the working-age population by age, sex, geography in 2019.

OBJECTIVE: Occupational ergonomic factors (OEF) include physical exertion, demanding posture, repetitive work, hand-arm vibration, kneeling or squatting, rising, and climbing, which are risk factors for low-back pain (LBP). This study aimed to examine the prevalence, years lived with disability (YLD), healthcare costs, and productivity losses of LBP attributable to OEF by age, sex, World Health Organization region, and country in 2019. METHODS: In this cross-sectional study, prevalence and YLD were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Employment statistics were obtained from the International Labor Organization websites. Health and economic impact was estimated for 192 countries and territories using the population attributable fraction method. RESULTS: Globally, OEF were responsible for 126.1 million prevalent cases of LBP and 15.1 million YLD in the working-age population (aged 15-84 years) in 2019, with the Western Pacific region suffering most. OEF-attributable LBP led to $216.1 billion of economic losses worldwide. Of these, $47.0 billion were paid in healthcare costs, with the public sector serving as the largest contributor (59.2%). High-income countries bore >70% of global economic burden, whereas middle-income countries experienced >70% of global YLD. Generally, more prevalent cases and healthcare costs were found among females, whereas more YLD, productivity losses, and total costs were found among males. CONCLUSIONS: Globally, OEF-attributable LBP presented a heavy burden on health and economic systems. Exercise together with education, active monitoring, evidence-based medical practices, alternative cost-effective solutions, and prioritizing health policies are needed.

Analysis of the clinical outcomes of microbial contamination caused by environmental contamination of the embryology laboratory during IVF-ET treatment cycles.

BACKGROUND: Bacterial contamination may cause loss of or damage to cultured oocytes or embryos, resulting in the lack of transplantable embryos during IVF embryo culture. However, there are few reports about IVF embryo contamination caused by embryology laboratories. In this work, we evaluated clinical pregnancy outcomes and the risk of maternal and infant complications after embryo contamination caused by environmental pollution during IVF. METHODS: The authors retrospectively analyzed 2490 IVF-ET ovulation induction therapy cycles in the Reproductive Center of Yichang Central People's Hospital from January 2015 to May 2022. According to the presence or absence of embryo culture medium contamination, the two groups were divided into an embryo contamination cycle and a nonembryo contamination cycle. The primary outcome parameters were the characteristics and progress of embryo culture medium contamination. Embryo laboratory outcomes, pregnancy outcomes, and maternal and infant complications were secondary outcome parameters. RESULTS: One case of embryo contamination originated from semen contamination. The remaining 15 cases involved environmental contamination outbreaks in embryo culture chambers, caused by Staphylococcus pasteuri. Compared with conventional uncontaminated IVF cycles, the 15 cases of contaminated embryo cycles showed no significant difference in embryo laboratory outcomes, pregnancy outcomes, or maternal and infant complications except for a slightly higher rate of fetal growth retardation. Ultimately, 11 live-born infants were successfully delivered, of which 2 were premature. The remaining 4 patients did not become pregnant after 1-2 transfers due to a lack of transferable embryos. CONCLUSION: When the embryo culture medium is contaminated due to the environmental contamination of the IVF culture room, it is feasible to perform daily rapid rinsing of the culture medium and avoid blastocyst culture as remedial treatment. However, the long-term impact on offspring needs further prospective research.

Health and Economic Outcomes Associated With Musculoskeletal Disorders Attributable to High Body Mass Index in 192 Countries and Territories in 2019.

Importance: The degree to which health and economic outcomes of musculoskeletal disorders are attributable to high body mass index (BMI) has not been quantified on a global scale. Objective: To estimate global health and economic outcomes associated with musculoskeletal disorders-low back pain (LBP), gout, and osteoarthritis attributable to high BMI in 2019. Design, Setting, and Participants: This cross-sectional study used data of 192 countries and territories from the Global Burden of Diseases, Injuries, and Risk Factors Study, World Health Organization Global Health Expenditure, World Bank, and International Labour Organization databases. Data analyses were conducted from February 24 to June 16, 2022. Main Outcomes and Measures: Prevalence, years lived with disability (YLDs), health care costs, and productivity losses due to morbidity from LBP, gout, and osteoarthritis attributable to high BMI by region and country. Prevalence and YLDs were calculated with the population attributable fraction approach. The economic burden, including health care costs and productivity losses due to morbidity, was also quantified. Health care costs borne by the public, private, and out-of-pocket sectors were estimated based on their corresponding payment shares. Productivity losses were estimated based on the output per worker. A sensitivity analysis was conducted to arrive at the base, minimum, and maximum estimates (ie, uncertainty interval [UI]) by using the mean, lower, and upper bounds of all input variables. Results: High BMI was estimated to be responsible for 36.3 million (UI, 18.4-61.0 million), 16.9 million (UI, 7.5-32.5 million), and 73.0 million (UI, 32.4-131.1 million) prevalent cases of LBP, gout, and osteoarthritis, respectively, which accounted for 7.3 million (UI, 3.0-15.0 million) YLDs across 192 countries and territories in 2019. Globally, the YLDs of musculoskeletal disorders attributable to high BMI accounted for 1.0% of all-cause YLDs in the working-age population aged 15 to 84 years. The global total costs of musculoskeletal disorders attributable to high BMI reached $180.7 billion (UI, $83.8-$333.1 billion), including $60.5 billion (UI, $30.7-$100.5 billion) in health care costs and $120.2 billion (UI, $53.1-$232.7 billion) in productivity losses. In terms of the global health care costs, 58.9% ($35.6 billion; UI, $17.8-$59.6 billion) was borne by the public sector, 24.0% ($14.5 billion; UI, $7.8-$23.2 billion) by the private sector, and 17.1% ($10.3 billion; UI, $5.1-$17.6 billion) by the out-of-pocket sector. On average, the total costs accounted for 0.2% of global gross domestic product. Great inequalities in the disease and economic burden existed across regions and countries. Nearly 80% of global health care (82.4%) and morbidity-related costs (82.9%) were paid by high-income countries, whereas more than 60% (61.4%) of global YLDs occurred in middle-income countries. Conclusions and Relevance: In this cross-sectional study of 192 countries and territories, a substantial amount of the health and economic impact of musculoskeletal disorders was attributable to high BMI. Developing effective policies and active participation from health professionals to prevent excessive weight gain are needed. More available estimates are also needed to facilitate a global analysis.

Trends in Musculoskeletal Rehabilitation Needs in China From 1990 to 2030: A Bayesian Age-Period-Cohort Modeling Study.

Background: Disability and medical expenses caused by musculoskeletal disorders in China had a great impact on the global health and economy. Rehabilitation is essential for dealing with musculoskeletal disorders. However, China's musculoskeletal rehabilitation needs remain unknown. This study aimed to examine the secular trends for musculoskeletal rehabilitation needs in China from 1990 to 2030. Methods: Data on musculoskeletal rehabilitation needs were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) repository. Estimated annual percentage changes (EAPCs) were calculated to reflect fluctuations in the age-standardized rates. The Bayesian age-period-cohort models were used to project rehabilitation needs. Results: The number of prevalent cases and years lived with disability (YLD) counts in need of musculoskeletal rehabilitation increased greatly in China from 1990 to 2019. There will be 465.9 million Chinese people in need of rehabilitation, with the age-standardized prevalence rate increasing to 21,151.0 [2.5-97.5% predictive interval (95% PI) 14,872.6-27,429.3] per 100,000 persons in 2030. Similarly, the YLD counts will increase to 40.1 million, with the age-standardized YLD rate increasing to 1,811.2 (95% PI 1,232.5-2,390.0) per 100,000 persons in 2030. Conclusions: Increasing trends in musculoskeletal rehabilitation needs were found from 1990 to 2019, which will be anticipated through 2030. Rehabilitation is suggested to be integrated into primary care settings.

Secular Trends in Musculoskeletal Rehabilitation Needs in 191 Countries and Territories From 1990 to 2019.

Importance: It is hard for policy makers and health professionals to develop musculoskeletal rehabilitation strategies because secular trends for musculoskeletal rehabilitation by region and country remain unknown. Objective: To evaluate the secular trends in global musculoskeletal rehabilitation needs by sex, age, region, country, and health condition. Design, Setting, and Participants: This cross-sectional study included data from 191 countries and territories from the World Health Organization Rehabilitation Need Estimator between January 1, 1990, and December 31, 2019. Data analyses were performed from February to May 2021. Main Outcomes and Measures: Prevalence and years lived with disability (YLDs) of musculoskeletal disorders in need of rehabilitation, overall and by sex, age, region, country, and health condition. Trends in rehabilitation needs were evaluated by the estimated annual percentage changes (EAPCs) in age-standardized rates. Pearson correlation analysis was used to examine the associations between EAPCs and the age-standardized rates in 1990. The associations between the age-standardized rates and universal health coverage (UHC) effective coverage index were assessed by fitting a restricted cubic spline in a linear model. Results: From 1990 to 2019, the global number of prevalent cases of musculoskeletal disorders in need of rehabilitation increased from 1060.6 (95% uncertainty interval [UI], 1009.1-1116.4) million to 1713.6 (95% UI, 1632.4-1800.4) million, with a steady increase in the number of YLDs from 93.9 (95% UI, 67.7-123.6) million to 149.0 (95% UI, 107.5-198.6) million. Overall, 55 countries and territories (28.8%) had annual increase in age-standardized prevalence rates, and 18 countries and territories (9.4%) had annual increase in YLD rates. The global age-standardized prevalence and YLD rates of musculoskeletal disorders decreased annually with EAPCs of 0.34 (95% CI, -0.37 to -0.31) and 0.42 (95% CI, -0.51 to -0.32), respectively. Specifically, the global age-standardized prevalence and YLD rates decreased for low back pain (prevalence: EAPC, -0.52; 95% CI, -0.57 to -0.47; YLD: EAPC, -0.52; 95% CI, -0.66 to -0.37), fractures (prevalence: EAPC, -0.35; 95% CI, -0.41 to -0.30; YLD: EAPC, -0.42; 95% CI, -0.65 to -0.19), other injuries (prevalence: EAPC, -0.75; 95% CI, -0.82 to -0.68; YLD: EAPC, -1.04; 95% CI, -1.38 to -0.71), and amputation (prevalence: EAPC, -0.64; 95% CI, -0.73 to -0.55; YLD: EAPC, -1.13; 95% CI, -1.60 to -0.65). The age-standardized prevalence rate decreased for neck pain (EAPC, -0.10; 95% CI, -0.18 to -0.02) but increased for osteoarthritis (EAPC, 0.13; 95% CI, 0.06-0.19) and rheumatoid arthritis (EAPC, 0.37; 95% CI, 0.04-0.70). In contrast, the age-standardized YLD rates remained stable for neck pain (EAPC, -0.09; 95% CI, -0.35 to 0.16), osteoarthritis (EAPC, 0.14; 95% CI, -0.14 to 0.42), and rheumatoid arthritis (EAPC, 0.38; 95% CI, -0.40 to 1.16). The age-standardized prevalence rate of neck pain decreased faster in male individuals, with an EAPC of -0.10 (95% CI, -0.19 to -0.02), while the age-standardized prevalence rate of low back pain decreased faster in female individuals, with an EAPC of -0.55 (95% CI, -0.60 to -0.51). EAPCs were significantly associated with the baseline age-standardized rates (prevalence: ρ = -0.49; P < .001; YLD: ρ = -0.55; P < .001), except for those of neck pain and rheumatoid arthritis. Excess rehabilitation needs were observed in countries with both higher and lower UHC effective coverage indexes (prevalence: ß = 749.04; SE, 288.52; P = .01; YLD: ß = 49.70; SE, 22.89; P = .03). Conclusions and Relevance: In this cross-sectional study, substantial increases in musculoskeletal rehabilitation needs were found across locations, suggesting rehabilitation needs have become a global health concern. Mitigating risk factors, strengthening rehabilitation in primary health care, and allocating sufficient funds are encouraged to satisfy rehabilitation needs.

Psychometric properties of the traditional Chinese version of the youth attitude to noise scale: a cross-sectional study in a large representative sample.

OBJECTIVES: This study aimed to examine the psychometric properties of the traditional Chinese version of the Youth Attitude to Noise Scale (YANS) in a large representative sample. DESIGN: Cross-sectional study. SETTING: 15 secondary schools in Hong Kong, China. PARTICIPANTS: 2842 adolescents aged 12-20 years participated in this study between April and July 2016. METHODS: The standard forward-backward validation procedures were followed to obtain the traditional Chinese version of the YANS. Prior to the formal investigation, the YANS was evaluated by cognitive debriefing. The sample was randomly divided into two halves for exploratory factor analyses (EFAs) and confirmatory factor analyses (CFAs), respectively. The number of factors was determined by comparison data approach using EFAs, and the factor structure was confirmed by CFAs using the one-factor, four-factor and bifactor models. The scale's internal reliability, dimensionality and measurement invariance across gender and age groups were also examined. RESULTS: EFAs (n=1338) showed that four factors were extracted, and CFAs (n=1337) demonstrated the bifactor model fitted better to the sample than the other models. Additionally, the traditional Chinese version of the YANS showed high reliability (ω=0.84), a general factor, scale multidimensionality, and gender and age invariance. CONCLUSIONS: The findings of the current study indicate that the traditional Chinese version of the YANS is a feasible instrument to assess attitude to noise in Chinese adolescents, regardless of their gender and age. Given the presence of a general factor, the YANS is not merely multidimensional, and whether to use the total or subscale scores is recommended to rely on research objectives.

Association between Non-Restorative Sleep and Quality of Life in Chinese Adolescents.

To examine non-restorative sleep and its impact on quality of life (QOL) in Chinese adolescents, this cross-sectional study included 2827 students aged 12-20 who were selected from 15 secondary schools in Hong Kong, China. Non-restorative sleep was assessed by a single item, rated on a 0-10 scale: "To what extent did you feel refreshed upon awakening over the past month?". QOL was evaluated by the World Health Organization Quality of Life Measure-Abbreviated Version Hong Kong Chinese Version. Univariable and multivariable linear mixed-effects regressions were conducted to examine the influence of non-restorative sleep (NRS) on QOL. In the present sample, the mean overall QOL was 13.83, and the extent of feeling refreshed upon awakening was 4.75 on average. In multivariable linear mixed-effects regression, one unit feeling less refreshed upon awakening was associated with 0.37 units of poorer overall QOL after adjusting for age, gender, medical conditions, parental education and occupation, weekly hours of aerobic exercises, smoking and drinking habits. Additionally, adolescents with a significantly poorer overall QOL were more likely to be older, have medical problems, have parents with an educational level of primary school or below, have an unemployed father, engage in less weekly aerobic exercise, and be current smokers or former drinkers. Adolescents who experienced non-restorative sleep had a poorer QOL. Future studies are needed to alleviate non-restorative sleep to improve health outcomes in adolescents.

Mental health status compared among rural-to-urban migrant, urban and rural school-age children in Guangdong Province, China.

BACKGROUND: Previous research has documented mental health status among rural-to-urban migrant children (labeled as "migrant children" henceforth) and urban children. However, the findings remain unclear. In addition, far less attention has been paid to rural children's psychological outcomes. The purpose of this study was to compare mental health status among migrant, urban and rural school-age children in Guangdong Province, China. METHODS: This was a cross-sectional study involving 372 migrant, 254 urban and 268 rural children selected respectively from 3 private schools, 4 public schools and 2 village schools in Guangdong Province, China. Participants provided their socio-demographic information and completed the Strengths and Difficulties Questionnaire (SDQ) to assess mental health. One-way analyses of variance (ANOVAs) and Bonferroni post hoc test were used to evaluate SDQ scores differences. A multiple linear regression analysis was conducted to measure mental health differences among children after controlling for socio-demographics. Chi-square analyses were used to assess differences in the prevalence of mental health problems among children. RESULTS: Bonferroni post hoc test showed that migrant and rural children reported significantly higher scores than urban peers in emotional symptoms, hyperactivity/inattention and total difficulties score (p < 0.01). In addition, migrant children reported a higher peer problems score compared to urban children (p < 0.001). In multiple linear regression analysis, rural and migrant children reported significantly a higher total difficulties score than urban children (p = 0.046 and 0.024, respectively). Additionally, female gender, having insurance, seldom communicating with parents, and higher monthly household income were negatively associated with a higher total difficulties score. Conversely, children's father with secondary education was positively associated with a higher total difficulties score. The prevalence of mental health problems among rural, migrant and urban children were 26.5, 18.8 and 15.0% (χ2 = 11.41, p = 0.003), respectively. CONCLUSIONS: Rural and migrant children reported poorer mental health than urban children. Female gender, having insurance, seldom communicating with parents, and higher monthly household income were associated with better mental health of children. However, children's father with secondary education was associated with poorer mental health of children. Given the different effects of socio-demographics, further support might be provided accordingly to improve the mental health of school-age children.

Chronic hypoxia in pregnancy affected vascular tone of renal interlobar arteries in the offspring.

Hypoxia during pregnancy could affect development of fetuses as well as cardiovascular systems in the offspring. This study was the first to demonstrate the influence and related mechanisms of prenatal hypoxia (PH) on renal interlobar arteries (RIA) in the 5-month-old male rat offspring. Following chronic hypoxia during pregnancy, phenylephrine induced significantly higher pressor responses and greater vasoconstrictions in the offspring. Nitric oxide mediated vessel relaxation was altered in the RIA. Phenylephrine-stimulated free intracellular calcium was significantly higher in the RIA of the PH group. The activity and expression of L-type calcium channel (Cav1.2), not T-type calcium channel (Cav3.2), was up-regulated. The whole-cell currents of calcium channels and the currents of Cav1.2 were increased compared with the control. In addition, the whole-cell K(+) currents were decreased in the offspring exposed to prenatal hypoxia. Activity of large-conductance Ca(2+)-activated K(+) channels and the expression of MaxiKα was decreased in the PH group. The results provide new information regarding the influence of prenatal hypoxia on the development of the renal vascular system, and possible underlying cellular and ion channel mechanisms involved.

Prenatal exposure to hypoxia induced Beclin 1 signaling-mediated renal autophagy and altered renal development in rat fetuses.

AIMS: Hypoxia has adverse effects on renal development. This study was the first to test hypoxia-induced renal autophagy in rat fetuses. METHODS: Pregnant rats were exposed to hypoxia or normoxia during pregnancy and fetal kidneys were collected at gestation day 21. RESULTS: Fetal kidney weight and ratio of kidney-body weight were reduced. Histological analysis showed enlargement in Bowman space and wider space between interstitia in the kidneys of fetus exposed to hypoxia. Fetal renal B-cell lymphoma 2 (BCL-2) was decreased accompanied with higher 2'-deoxyuridine 5'-triphosphate nick end-labeling staining and unchanged soluble FAS in the hypoxia group. Hypoxia increased autophagic structures, including autophagosomes and autolysosomes, in fetal kidneys and increased renal APG5L. There was an increase in renal LC3-II, Beclin 1, p-S6, hypoxia inducible factor 1α (HIF-1a), and ratio of LC3-II-LC3-I and a decrease in P62, protein kinase B (AKT), and phosphorylated AKT in the hypoxia group. Both renal mammalian target of rapamycin (mTOR) and Beclin 1 signaling were upregulated. CONCLUSION: Hypoxia-affected fetal renal development was associated with renal apoptosis and Beclin 1 signaling-mediated autophagy.

Hippocampal apoptosis involved in learning deficits in the offspring exposed to maternal high sucrose diets.

The hippocampus plays a crucial role in learning and memory, and neuronal apoptosis in the hippocampus contributes to learning deficits. Metabolism problems in pregnancy related to excessive fuel consumption (e.g., high fat, high sugar) may influence cognitive and behavioral functions in the offspring by affecting developing brain cells. This study determined the influence of maternal high sucrose (HS) diets on behavior and hippocampal neurons in the young offspring. The ratio of brain weight to body weight in the offspring exposed to prenatal HS diets was significantly decreased; the Morris water maze showed that the offspring exposed to prenatal HS diets exhibited increased escape latencies and path length during navigation testing, while there were no changes in time spent in the target quadrant and number of target approaches. In the offspring exposed to prenatal HS, TUNEL-positive cells were significantly increased in CA1, CA2 and CA3 of the hippocampus; protein expression of insulin-like growth factor-I, PI3K and phosphorylated Akt was significantly decreased, while caspase-3 and N-methyl-d-aspartate receptors were significantly increased in the hippocampus, and there was no change in expression of Bcl-2 and Akt. The results demonstrated that prenatal HS diets could induce the spatial acquisition deficits in the young offspring associated with hippocampal apoptosis, and altered signaling factors for antiapoptosis in the hippocampus might play a critical role in cognition disorders in young children.

High-salt diets during pregnancy affected fetal and offspring renal renin-angiotensin system.

Intrauterine environments are related to fetal renal development and postnatal health. Influence of salty diets during pregnancy on renal functions and renin-angiotensin system (RAS) was determined in the ovine fetuses and offspring. Pregnant ewes were fed high-salt diet (HSD) or normal-salt diet (NSD) for 2 months during middle-to-late gestation. Fetal renal functions, plasma hormones, and mRNA and protein expressions of the key elements of renal RAS were measured in the fetuses and offspring. Fetal renal excretion of sodium was increased while urine volume decreased in the HSD group. Fetal blood urea nitrogen was increased, while kidney weight:body weight ratio decreased in the HSD group. The altered ratio was also observed in the offspring aged 15 and 90 days. Maternal and fetal plasma antidiuretic hormone was elevated without changes in plasma renin activity and Ang I levels, while plasma Ang II was decreased. The key elements of local renal RAS, including angiotensinogen, angiotensin converting enzyme (ACE), ACE2, AT1, and AT2 receptor expression in both mRNA and protein, except renin, were altered following maternal high salt intake. The results suggest that high intake of salt during pregnancy affected fetal renal development associated with an altered expression of the renal key elements of RAS, some alterations of fetal origins remained after birth as possible risks in developing renal or cardiovascular diseases.

Angiotensin II-mediated vascular changes in aged offspring rats exposed to perinatal nicotine.

This study determined the long-term influence of prenatal nicotine exposure (PN) on blood pressure and vascular functions in the aged offspring rats. PN did not affect body weight and plasma adrenocorticotropic hormone level; however, it significantly reduced plasma angiotensin I and angiotensin II in both sexes. Systolic pressure in the male aged PN offspring was significantly higher. Angiotensin II-increased mean arterial pressure was higher in the aged PN offspring than that in the control regardless of sex. AT1 receptor blocker losartan, not AT2 receptor antagonist PD123319, reduced blood pressure in the aged PN rats more than that in the control. In the aged PN offspring, angiotensin II-increased vessel contraction and intracellular calcium level were higher in small mesenteric arteries. Acetylcholine-mediated vascular relaxation was weaker, and nitric oxide-related endothelial functions were damaged in aortic rings of PN offspring. Thickness of the wall of mesenteric arteries was increased in the male aged PN offspring. Ratio of AT1/AT2 receptors was significantly increased in the vessel of the PN group regardless of sex. These data provide new information on the very long term influence of PN on vascular structures and functions in the aged offspring, demonstrate that the aged PN female rats were not free of vascular risks after menopause, and suggest that multiple pathways may be involved in the detrimental alterations of the cardiovascular system of the PN rats.