Blood Pressure Dysregulation Research Articles

The role of adipose tissue in the regulation and dysregulation of blood pressure: a conceptual narrative review

The role of adipose tissue in the regulation and dysregulation of blood pressure: a conceptual narrative review

#2649 Blood pressure tend to decrease following COVID-19 infection in patients with chronic kidney disease—lessons learned from a community based cohort

Abstract Background and Aims Pre-existing hypertension (HTN) has been implicated as one of the most common co-morbidities in COVID-19 patients, likely contributing to disease severity. Additionally, the port of viral entry to the host cell—ACE2 receptor, which is a part of the renin-angiotensin-aldosterone system, was initially thought to cause blood pressure (BP) dysregulation. Recently, several large cohorts have been published, connecting COVID-19 infection to new-onset HTN. Nevertheless, the association of HTN with COVID-19 in patients with chronic kidney disease (CKD) in a community setting has not been fully elucidated. We aimed to study the effect of COVID-19 infection on BP in patients with CKD. Method In this cohort study we utilized the Maccabi Healthcare Services (MHS) database during the COVID-19 pandemic. MHS is a nationwide health care payer-provider, providing health services to approximately 2.6 million Israelis. Data is automatically collected and includes comprehensive laboratory results from a single central lab, full pharmacy prescription and purchase data, physician visits, vital signs documentation, imaging and extensive demographic information on each patient. The database includes several automatically formulated registries including a well validated CKD registry. On July 31st 2023 we looked at point prevalence of patients registered as having CKD stages I-V, defined as eGFR <60 ml/min and/or albuminuria over 30 mg on 24 hour urine collection or 30 mg/g creatinine on urine albumin to creatinine ratio, or proteinuria above 150 mg either at spot urine protein to creatinine ratio or over 24 hour collection. We included CKD patients over the age of 18 years, who had mostly mild COVID-19 disease, detected by SARS-CoV-2 PCR or antigen test between January 1st 2020 and December 31st 2022. Examinees were included only if they had at least one blood pressure measurement documented, in their primary care clinic, in the year prior to infection, and at least one measurement during the 12 months period following COVID-19. Only the 1st documented COVID-19 infection of each patient was included. We compared the differences in BP values between pre and post COVID-19. Results Out of 1,821,685 adults at Maccabi HMS in 2023, 193,566 patients were registered as having CKD. Of those, 86,618 had a documented first COVID-19 infection between the years 2020-2022, and 44,410 of them had documented BP measurements both prior and after COVID-19 were analyzed. Mean age for all CKD patients who had COVID-19 was 69.2 (SD-12.9) years and 22,151 (49.9%) were males. Most patients had CKD stage III—26,939 (60%), and 535 (1.2%) were on dialysis. Not surprisingly, 76% of CKD patients had a preexisting diagnosis of HTN and 44% had diabetes mellitus. Average BP values during the year prior to COVID-19 were 133/76.5 mmHg (SD 14.8 and 8.55, respectively). Mean BP values post COVID-19 were 132/75/9 mmHg (SD 15.5 and 8.9, respectively). This translates into a reduction of 1 mmHg in systolic BP and 0.6 mmHg in diastolic BP in the year prior to COVID-19 infection as compared with pre-covid-19 infection (P-value 0.03 and 0.004, respectively). Conclusion Contrary to previous studies, that linked COVID-19 infection to a higher set-point of BP, our data demonstrates in a large community-based cohort of CKD patients, that BP does not increase and even trends down following COVID-19. As patients were one year older during their post-covid year, and some had withdrew ACE inhibitors or ARB, due to erroneous fear of adverse effect on Covid-19 infectivity, we believe that our results may even underestimate the extent of decrease in BP. Further investigation might reveal the possible mechanisms related to this favorable BP decrease after COVID-19 infection, in CKD patients.

Cardiovascular disease: extraintestinal manifestation of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a spectrum of diseases characterized by the interplay of the aberrant immune system, genetic factors, environmental factors, and intestinal microbiota, resulting in relapsing inflammation of the gastrointestinal tract. Underlying pro-inflammatory state and immune dysregulation act as a catalyst for increasing the likelihood of developing extraintestinal manifestations, including cardiovascular diseases (CVD) like atherosclerosis, pericarditis, myocarditis, venous and arterial thromboembolism, arrhythmias, despite a lower prevalence of classic CVD risk factors, like high body mass index or dyslipidemia compared to the general population. Chronic inflammation damages endothelium resulting in the recruitment of inflammatory cells, which induce cytotoxicity, lipoprotein oxidation, and matrix degradation, which increases the risk of atherosclerosis. Additionally, intestinal dysbiosis disrupts the intestinal mucosal barrier, releasing endotoxins and lipopolysaccharides into circulation, further exaggerating the atherosclerotic process. Abnormal collagen metabolism and alteration of nitric oxide-mediated vasodilation lead to blood pressure dysregulation in patients with IBD. Therefore, it is essential to make lifestyle modifications like smoking cessation, dietary changes, and increasing physical activity with adherence to medication to mitigate the risk of developing CVD in patients with IBD. This article reviews the potential links between IBD and the increased risk of CVD in such individuals.

A Single Bout of Prolonged Sitting Augments Very Short-Term Blood Pressure Variability.

More habitual time spent engaging in prolonged sedentary behaviors increases the risk of developing hypertension. Beat-by-beat systolic (SBPV) and diastolic blood pressure variability (DBPV) are more pronounced in persons with hypertension and may be an early manifestation of blood pressure dysregulation. We tested the hypothesis that a single bout of prolonged sitting augments very short-term SBPV and DBPV. The secondary aim was to explore sex differences in prolonged sitting-induced increases in SBPV and DBPV. Thirty-three adults (22.9 ± 1.9 years; 17 females) completed a single, 3-hour bout of prolonged sitting with beat-by-beat arterial pressure determined at baseline, 1.5-hour, and 3-hour via finger photoplethysmography. There were no sex differences observed for baseline brachial SBP (males: 122 ± 10 mm Hg; females: 111 ± 9 mm Hg), SBPV (males: 1.87 ± 0.63 mm Hg; females: 1.51 ± 0.38 mm Hg), DBP (males: 68 ± 6 mm Hg; females: 66 ± 8 mm Hg), or DBPV (males: 1.40 ± 0.41 mm Hg; females: 1.27 ± 0.32 mm Hg) (all, P > 0.41). In the pooled sample, baseline SBPV (1.68 ± 0.54 mm Hg) remained unchanged after 1.5 hours (1.80 ± 0.60 mm Hg; P = 0.59) but increased after 3.0 hours (1.84 ± 0.52 mm Hg; P = 0.01). This post-sitting increase was driven by males (P = 0.009), with no difference observed in females (P = 1.00). Similarly, baseline DBPV (1.33 ± 0.36 mm Hg) was similar after 1.5 hours (1.42 ± 0.41 mm Hg; P = 0.72) but was increased at 3 hours (1.50 ± 0.34 mm Hg; P = 0.02). However, no sex differences in DBPV (all, P > 0.07) were observed across the time points. In young, normotensive adults, a single bout of prolonged sitting augmented beat-by-beat blood pressure variability, which may provide a link between uninterrupted sitting and the development of blood pressure dysregulation.

Chronic circadian stress raises mean arterial pressure in male, but not female, Bmal1-knockout rats

Shiftwork and other forms of circadian disruption are associated with an increased risk of cardiovascular and kidney disease, however, the mechanisms driving these associations have yet to be elucidated. It has been suggested that dyssynchrony between the endogenous molecular clock and the external environment during shiftwork may be connected with the development of cardiorenal pathologies and the dysregulation of blood pressure (BP). Brain and muscle arntl-like protein 1, or Bmal1, is a core component of the molecular clock. Loss of Bmal1 in both male and female rats results in lower BP compared to wild-type (WT) littermate controls. We hypothesized that Bmal1 is necessary for the acclimation to circadian stress induced by chronic circadian stress (CCS). Telemeters were surgically implanted in the abdominal aorta of 12-14 week old rats. After a 2 week recovery, animals were placed in a light-controlled room on a 12:12hr light/dark cycle. After 1 week acclimation, lights were phase-advanced 6hrs every week for 4 weeks. Telemetry data was collected for 2 minutes every 10 minutes each hour at 1000 samples/second and analyzed using cosinor analysis. The MESOR of mean arterial pressure (MAP) was similar pre- and post- CCS in male WT rats (n=8, 107±1 vs. 109±1 mmHg; 2-way ANOVA, p>0.05) and in female WT rats (n=9, 110±1 vs. 112±2 mmHg; p>0.05). Male Bmal1-KO rats (n=9) had higher MAP MESOR after CCS (103±1 vs 108±1mmHg; p<0.05), but female Bmal1-KO rats (n=6) had no change in MAP MESOR after CCS (100±2. vs 100±2 mmHg, p>0.05). MAP amplitude was similar between WT and KO males before- (6.5±0.7 vs. 5.2±0.8 mmHg) and after-CCS (5.1±0.4 vs. 5.3±0.4 mmHg, p>0.05). WT and KO females had similar MAP amplitude before- (7.2±0.6 vs 5.5±0.9 mmHg) and after-CCS (5.7±1.1 vs. 5.6±0.6, p>0.05). In summary, loss of Bmal1 combined with circadian stress resulted in higher BP in a sex- dependent manner. Despite having lower blood pressures pre-CCS, male Bmal1-KO rats had higher MAP after CCS while female Bmal1-KO rats were protected from increased BP. This suggests that Bmal1, a crucial component of the molecular clock, has a sex-specific role in BP regulation and the response to stress. This work is supported by NIH TL1DK139566-01. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of Heavy Alcohol Use on Nighttime Blood Pressure, Sleep Quality, and Urine Catecholamines

Heavy alcohol drinking habits contribute to the development of hypertension; this is partly due to overactivation of the sympathetic nervous system and the increased release of catecholamines. Recently, heavy alcohol drinking has been linked to poor sleep quality, but the underlying mechanisms remain unclear. We postulated that long-term frequent heavy alcohol use could increase catecholamine levels and cause blood pressure dysregulation at night, altogether influencing sleep quality. Therefore, the purpose of this study is to test the following hypothesis that compared to non-heavy drinkers, heavy drinkers have a higher level of nighttime catecholamines, a higher levels of nighttime blood pressure, and poorer sleep quality. A total of 44 men and postmenopausal women non-smokers, free of major clinical diseases, were included in this study. Heavy drinkers were defined as those having a dried blood spot phosphatidylethanol (PEth, a biomarker to detect heavy alcohol drinking) level ≥ 20 ng/mL. Participants wore an ambulatory blood pressure monitor for 24 hours and catecholamines were measured from urine samples collected in the same 24-hour period. Sleep quality was measured by using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. There were 21 heavy drinkers (mean±SEM for age: 58±1 and BMI: 26.2±0.7 kg/m2) and 23 non-heavy drinkers (age: 58±1 and BMI: 27.5±0.8 kg/m2; P≥0.3 vs. heavy drinkers). Compared to non-heavy drinkers, heavy drinkers had a higher nighttime systolic blood pressure (SBP), higher diastolic blood pressure (DBP), and a lower SBP dipping ratio (heavy drinkers vs. non-heavy drinkers for nighttime SBP: 118±3 vs. 109±2 mmHg, P=0.02; nighttime DBP: 70±2 vs. 65±2 mmHg, P=0.04; and SBP dipping ratio: 10.6±1.4% vs. 14.5±1.6%, P=0.04). No differences were found in nighttime urine catecholamines between heavy drinkers and non-heavy drinkers (P≥0.3). A total of 13 participants had a PSQI score higher than 5, indicating poor sleep quality; however, PSQI scores were similar between heavy and non-heavy drinkers (P=0.8). These findings indicate that heavy drinkers had a higher nighttime blood pressure and are consistent with the observation that heavy drinking is associated with an increased risk of hypertension in mid-life adults. Interestingly, the increase in nighttime blood pressure does not appear to be related to catecholamines and sleep quality in apparently healthy mid-life adults does not appear to be influenced by heavy drinking habits. This work was supported by NIAAA AA028537 to CLH and AHA 1266805160 to TH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sleep Duration Irregularity is Associated with Elevated Blood Pressure During Submaximal Exercise in Young Adults.

Irregularity in nightly sleep duration is reported to associate with elevated blood pressure (BP), but it is unclear whether this association can be observed with BP measured during exercise after controlling for factors known to influence the exercise pressor reflex. Twenty-nine young adults (22±4y; 19 men, 10 women) performed cycling exercise until volitional fatigue to assess peak oxygen uptake (VO2). Actigraphy was used to monitor sleep duration and daily physical activity for seven consecutive days after which participants completed two bouts of moderate-intensity cycling while BP and VO2 were measured using a Tango+ device and indirect calorimetry, respectively. Systolic BP was averaged from the two bouts of exercise and expressed as a change from seated rest (∆SBP). Sleep duration regularity was calculated as standard deviation (SD) and coefficient of variation (CV). Systolic BP at seated rest, during exercise, and ∆SBP was 113±13, 152±21, and 38±13 mmHg, respectively. Sleep duration SD (range 10-146 min) and sleep duration CV (range 2-54%) when excluding weekend nights were significantly correlated with ∆SBP (r = 0.58 and r = 0.62, respectively; both p<0.01) after adjusting for age, sex, body mass index, peak VO2, physical activity, resting systolic BP, chronotype, and the VO2 response to exercise. Sleep duration regularity analyzed with weekend nights included (across all seven days) was also significantly correlated with ∆SBP (p≤0.01), but had weaker correlation coefficients. These results indicate that sleep regularity, especially when excluding weekend nights, is associated with the rise in systolic BP during moderate-intensity exercise in young adults. Sleep duration regularity may be a useful tool to capture the impact of intermittent nights of insufficient sleep on BP dysregulation.

Orthostatic Hypotension and Antihypertensive Treatment in Lung Transplant Recipients: A Cross-Sectional Study.

Lung transplant is the ultimate treatment of many end-stage lung diseases. Calcineurin inhibitors, crucial in immunosuppression for lung transplant recipients, are linked to secondary hypertension, necessitating antihypertensive treatment. In addition, lung transplant recipients frequently experience orthostatic hypotension, occasionally stemming from autonomic dysfunction, but also commonly attributed as a negative side effect of antihypertensive treatment. Our study aimed to evaluate the frequency of orthostatic blood pressure irregularities and investigate the involvement of antihypertensive treatment as a potential risk factor in the occurrence among lung transplant recipients. Fifty-six consecutive lung transplant recipients, both inpatient and outpatient, at the University Hospital Zurich (Switzerland) were monitored from 1999 to 2013. Transplant recipients underwent a Schellong test (an active standing test). Our evaluation encompassed their initial traits, such as the existence of supine hypertension. We computed the odds ratio for the comparison of the likelihood of experiencing orthostatic hypotension while using a minimum of 1 type of antihypertensive medication versus absence of antihypertensive drugs. Of the lung transplant recipients, 25% showed a positive Schellong test. Within this group, 64% had supine hypertension, and 29% displayed symptoms of orthostatic hypotension. Among the patients, 71% were using at least 1 type of antihypertensive medication. The odds ratio for showing orthostatic hypotension while taking at least 1 type of antihypertensive drug versus the absence of antihypertensive medications was 1.64 (95% exact CI, 0.39-6.90) with P = .50. This finding remained consistent regardless of age, sex, inpatient or outpatient status, and the duration since transplant. Orthostatic blood pressure dysregulation is prevalent among lung transplant recipients, frequently without noticeable symptoms. In our cohort, the use of antihypertensive medications did not elevate the risk of orthostatic hypotension.

Oral contraceptives in adolescents: a retrospective population-based study on blood pressure and metabolic dysregulation.

This study aimed to explore the relationship between oral contraceptive use and blood pressure values and in a national cohort of women adolescents and to investigate the level of coexistence of the high blood pressure levels, dyslipidemia or insulin resistance. This is a retrospective cohort study that evaluated data form 14,299 adolescents aged 14 to 17years. Crude and race-and age-adjusted analyses were performed using Poisson regression to estimate the prevalence ratios. Data clustering analysis was performed using machine learning approaches supported by an unsupervised neural network of self-organizing maps. We found that 14.5% (n = 2076) of the women adolescents use oral contraceptives. Moreover, an increased prevalence of high blood pressure, dyslipidemia, and insulin resistance (all P < 0.001) was observed among adolescents who use oral contraceptives as compared to those who do not. Our analysis also showed that 2.3% of adolescents using oral contraceptives had both high blood pressure levels and dyslipidemia, whereas 3.2% had high blood pressure levels combined with insulin resistance (all P < 0.001). The algorithmic investigative approach demonstrated that total cholesterol, LDLc, HDLc, insulin, and HOMA-IR were the most predicted variables to assist classificatory association in the context of oral contraceptive use among women adolescents with high blood pressure. These findings suggest that oral contraceptives were associated with an increased prevalence of high blood pressure, dyslipidemia, and insulin resistance among women adolescents. Although the indication of this therapy is adequate to avoid unintended pregnancies, their use must be based on rigorous individual evaluation and under constant control of the cardiometabolic risk factors.

Effect of combined hormone replacement therapy on sympathetic nervous system function in postmenopausal women – A cross-sectional study

Background: There is an increased prevalence of cardiovascular and metabolic diseases in postmenopausal women. Estrogen plays an important role in the regulation of blood pressure (BP) and autonomic function. Various hormone therapies are widely used in postmenopausal women, especially combination therapy of low-dose estrogen and progesterone. Hormone therapy might be useful not only in alleviating menopausal symptoms but help in reducing cardiovascular risk factors and improving quality of life. Aims and Objectives: The aim of the study is to study the effect of combined estrogen and progesterone hormone therapy on BP and sympathetic overactivity in postmenopausal women. Materials and Methods: The study included two groups of 50 women each. Group I included postmenopausal women of age 45–55 years who were taking combined hormone therapy while Group II included postmenopausal women of the same age group who were not on any replacement therapy heart rate and BP in resting state was noted in both the groups. Sympathetic function assessment was done by performing cold pressor test, handgrip test, and BP response to standing on all the participants. Statistical analysis was done using the student’s t-test. Results: There was a statistically significant difference in resting heart rate, BP, and sympathetic function tests in both groups. Conclusion: There is a facilitatory role of combined estrogen and progesterone therapy in menopausal women in reducing BP and sympathetic system dysregulation.

Circadian blood pressure dysregulation in children with obstructive sleep apnea.

Obstructive sleep apnea (OSA) adversely affects normal blood pressure (BP) and may disrupt circadian BP patterns. We sought to examine 24-hour circadian BP rhythms in children with OSA and healthy controls. Children 5-14 years with OSA and healthy controls underwent 24-hour BP monitoring and actigraphy to quantify sleep. Shape invariant statistical models compared circadian BP patterns (e.g. times of BP peaks, time arrived at peak BP velocity [TAPV]) in the OSA and control groups. The analytic sample included 219 children (mild OSA: n = 52; moderate-to-severe OSA (MS-OSA): n = 50; controls: n = 117). In the morning, the MS-OSA group had earlier TAPV for DBP than controls (51 minutes, p < 0.001). TAPV in the evening was earlier for the MS-OSA group than controls (SBP: 95 minutes, p < 0.001; DBP: 28 minutes, p = 0.028). At mid-day, SBP and DBP velocity nadirs were earlier for the MS-OSA group than controls (SBP: 57 minutes, p < 0.001; DBP: 38 minutes, p < 0.01). The MS-OSA group reached most BP values significantly earlier than controls; the largest differences were 118 minutes (SBP) and 43 minutes (DBP) (p < 0.001). SBP and DBP were elevated in the MS-OSA group (hours 18-21 and 7--12, respectively, p < 0.01) compared to controls. The MS-OSA group was prone to "non-dipping" compared to controls (SBP: odds ratio [OR] = 2.16, 95% CI: 1.09, 4.29; DBP: OR = 3.45, 95% CI: 1.21, 10.23). Children with MS-OSA had changes in circadian BP patterns, namely earlier TAPV and BP peaks and nadirs than controls. Circadian disturbances in BP rhythms may be key to mapping the natural history of BP dysregulation in children with OSA.

Cardiovascular dysfunction induced by combined exposure to nicotine inhalation and high-fat diet.

Smoking and high-fat diet (HFD) consumption are two modifiable risk factors for cardiovascular (CV) diseases, and individuals who are overweight or obese due to unhealthy diet are more likely to use tobacco products. In this study, we aim to investigate the combined effects of nicotine (the addictive component of all tobacco products) and HFD on CV health, which are poorly understood. C57BL/6N male mice were placed on either HFD (60 kcal% fat) or regular diet (22 kcal% fat) and exposed to air or nicotine vapor for 10-12 wk. CV function was monitored by echocardiography and radiotelemetry, with left ventricular (LV) catheterization and aortic ring vasoreactivity assays performed at end point. Mice on HFD exhibited increased heart rate and impaired parasympathetic tone, whereas nicotine exposure increased sympathetic vascular tone as evidenced by increased blood pressure (BP) response to ganglionic blockade. Although neither nicotine nor HFD alone or in combination significantly altered BP, nicotine exposure disrupted circadian BP regulation with reduced BP dipping. LV catheterization revealed that combined exposure to nicotine and HFD led to LV diastolic dysfunction with increased LV end-diastolic pressure (LVEDP). Moreover, combined exposure resulted in increased inhibitory phosphorylation of endothelial nitric oxide synthase and greater impairment of endothelium-dependent vasodilation. Finally, a small cohort of C57BL/6N females with combined exposure exhibited similar increases in LVEDP, indicating that both sexes are susceptible to the combined effect of nicotine and HFD. In summary, combined exposure to nicotine and HFD leads to greater CV harm, including both additive and new-onset CV dysfunction.NEW & NOTEWORTHY Nicotine product usage and high-fat diet consumption are two modifiable risk factors for cardiovascular diseases. Here, we demonstrate that in mice, combined exposure to inhaled nicotine and high-fat diet results in unique cardiovascular consequences compared with either treatment alone, including left ventricular diastolic dysfunction, dysregulation of blood pressure, autonomic dysfunction, and greater impairment of endothelium-dependent vasorelaxation. These findings indicate that individuals who consume both nicotine products and high-fat diet have distinctive cardiovascular risks.

Therapeutic mechanisms of ginseng in coronary heart disease.

Coronary heart disease (CHD) is the most common clinical manifestation of cardiovascular disease. It is characterized by myocardial ischemia, which is caused by coronary atherosclerosis. CHD is a significant global health problem with increasing prevalence every year because of significant changes in the lifestyles and diets. Ginseng is a traditional Chinese medicinal herb that has been used in food preparations and traditional medicine for several centuries. Several studies have demonstrated that ginseng improved cardiac function by normalizing blood glucose levels and decreasing blood pressure, oxidative stress, platelet aggregation, and lipid dysregulation in vivo. This review describes the current understanding of the mechanisms by which ginseng alleviates CHD, and provides a reference for the clinical development and application of ginseng as an alternative therapy for CHD.

Renal tubular SGK1 is required to achieve blood pressure surge and circadian rhythm.

Blood pressure (BP) follows a circadian pattern that rises during the active phase of the day (morning surge) and decreases during the inactive (night dipping) phase of the day. The morning surge coincides with increased circulating glucocorticoids and aldosterone, ligands for glucocorticoid receptors and mineralocorticoid receptors, respectively. Serum- and glucocorticoid-induced kinase 1 (SGK1), a clock-controlled and glucocorticoid receptor- and mineralocorticoid receptor-induced gene, plays a role in BP regulation in human and animal models. However, the role of SGK1 in BP circadian regulation has not yet been demonstrated. Using telemetry, we analyzed BP in the inducible renal tubule-specific Sgk1Pax8/LC1 model under basal K+ diet (1% K+) and high-K+ diet (HKD; 5% K+). Our data revealed that, under basal conditions, renal SGK1 plays a minor role in BP regulation; however, after 1 wk of HKD, Sgk1Pax8/LC1 mice exhibited significant defects in diastolic BP (DBP), including a blunted surge, a decreased amplitude, and reduced day/night differences. After prolonged HKD (7 wk), Sgk1Pax8/LC1 mice had lower BP than control mice and exhibited reduced DBP amplitude, together with decreased DBP day/night differences and midline estimating statistic of rhythm (MESOR). Interestingly, renal SGK1 deletion increased pulse pressure, likely secondary to an increase in circulating aldosterone. Taken together, our data suggest that 1) the kidney plays a significant role in setting the BP circadian rhythm; 2) renal tubule SGK1 mediates the BP surge and, thus, the day/night BP difference; 3) long-term renal SGK1 deletion results in lower BP in mutant compared with control mice; and 4) renal SGK1 indirectly regulates pulse pressure due to compensatory alterations in aldosterone levels.NEW & NOTEWORTHY Dysregulation of blood pressure (BP) circadian rhythm is associated with metabolic, cardiovascular, and kidney diseases. Our study provides experimental evidence demonstrating, for the first time, that renal tubule serum- and glucocorticoid-induced kinase 1 (SGK1) plays an essential role in inducing the BP surge. Inhibitors and activators of SGK1 signaling are parts of several therapeutic strategies. Our findings highlight the importance of the drug intake timing to be in phase with SGK1 function to avoid dysregulation of BP circadian rhythm.

Elevated Blood Pressure and Aldosterone Dysregulation in Young Black Women Versus White Women on Controlled Sodium Diets.

Black women have a higher prevalence of hypertension as compared to White women. Differences in dietary sodium intake have been implicated as a contributing factor for the disparities in hypertension. Our objective was to understand whether young Black women would have higher systolic blood pressure (SBP) than White women even on controlled sodium diets and to determine whether SBP differences were due to differences in dietary sodium intake and/or aldosterone regulation. The analyses included 525 hypertensive and normotensive women (ages 18-71) from the International Hypertensive Pathotype consortium, who were maintained on liberal sodium (LIB; >200 mEq sodium/day) and restricted sodium (RES; 10 mEq sodium/day) diets. Multivariate regression analyses (adjusted for age, race, study site, body mass index) found that Black women (ages 18-50) had significantly higher SBP than White women on both sodium diets: +8.7 ± 2.7 mmHg (P-value = .002) on a LIB diet and +8.5 ± 2.5 mmHg (P-value = .001) on a RES diet. Even among 18- to 35-year-olds-who were normotensive and nonobese-Black women had higher SBP: +7.9 ± 2.4 mmHg (P-value = .001) on a LIB diet and +7.6 ± 2.7 mmHg (P-value = .005) on a RES diet. Younger Black women also had higher plasma aldosterone concentration to plasma renin activity ratio (ARR) on both LIB and RES diets as well as a higher sodium-modulated aldosterone suppression-stimulation index-an indicator of aldosterone dysregulation. In younger Black women-but not in White women-there was a significant association between SBP and ARR on both LIB and RES diets. Young Black women had increased SBP and ARR as compared to White women on LIB and RES diets, which offers insights into the possible mechanisms for the increased hypertension and cardiovascular disease risk in an at-risk and understudied population.

A 3-year natural history of orthostatic blood pressure dysregulation in early Parkinson’s disease

In Parkinson’s disease (PD), cardiovascular dysautonomia accumulates with disease progression, but studies are lacking on the natural history behind each subtype except orthostatic hypotension. This study investigated the early natural history of orthostatic blood pressure (BP) subtypes in PD. Two hundred sixty-seven early PD patients were included. Their cardiovascular functions were assessed by head-up tilt-test and 123I-metaiodobenzylguanidine scintigraphy. All patients were classified as having supine hypertension (SH), orthostatic hypertension (OHT), delayed orthostatic hypotension (dOH), or orthostatic hypotension (OH) according to consensus criteria. The patients were assigned to one of three groups: extreme BP dysregulation (BPextreme), mild BP dysregulation (BPmild), and no BP dysregulation (BPnone) according to their orthostatic BP subtypes. The autonomic functions of 237 patients were re-assessed after approximately 3 years. Among initially enrolled subjects, 61.8% of the patients showed orthostatic BP dysregulation: 29.6% in the BPextreme group and 32.2% in the BPmild group. At follow-up, the BPextreme group increased in number, while the BPmild group diminished. Two-thirds of the initial BPextreme patients maintained their initial subtype at follow-up. In comparison, 40.7% of the initial BPmild patients progressed to the BPextreme group, and 32.4% and 14.7% of the initial BPnone group progressed to BPextreme and BPmild groups, respectively. Cardiac denervation was most severe in the BPextreme group, and a linear gradient of impairment was observed across the subtypes. In conclusion, various forms of positional BP dysregulation were observed during the early disease stage. SH and OH increased with disease progression, while OHT and dOH decreased, converting primarily to SH and/or OH.

Testosterone-associated blood pressure dysregulation in women with androgen excess polycystic ovary syndrome.

We tested the hypothesis that hyperandrogenemia in androgen excess polycystic ovary syndrome (AE-PCOS) is a primary driver in blood pressure (BP) dysregulation via altered sympathetic nervous system activity (SNSA), reduced integrated baroreflex gain and increased renin-angiotensin system (RAS) activation. We measured resting SNSA (microneurography), integrated baroreflex gain, and RAS with lower body negative pressure in obese insulin-resistant (IR) women with AE-PCOS [n = 8, 23 ± 4 yr; body mass index (BMI) = 36.3 ± 6.4 kg/m2] and obese IR controls (n = 7, control, 29 ± 7 yr; BMI = 34.9 ± 6.8 kg/m2), at baseline (BSL), after 4 days of gonadotropin-releasing hormone antagonist (ANT, 250 μg/day) and 4 days of ANT + testosterone (ANT + T, 5 mg/day) administration. Resting BP was similar between groups for systolic blood pressure (SBP; 137 ± 14 vs. 135 ± 14 mmHg, AE-PCOS, control) and diastolic BP (89 ± 21 vs. 76 ± 10 mmHg, AE-PCOS, control). BSL integrated baroreflex gain was similar between groups [1.4 ± 0.9 vs. 1.0 ± 1.3 forearm vascular resistance (FVR) U/mmHg], but AE-PCOS had lower SNSA (10.3 ± 2.0 vs. 14.4 ± 4.4 burst/100 heartbeats, P = 0.04). In AE-PCOS, T suppression increased integrated baroreflex gain, which was restored to BSL with ANT + T (4.3 ± 6.5 vs. 1.5 ± 0.8 FVR U/mmHg, ANT, and ANT + T, P = 0.04), with no effect in control. ANT increased SNSA in AE-PCOS (11.2 ± 2.4, P = 0.04). Serum aldosterone was greater in AE-PCOS versus control (136.5 ± 60.2 vs. 75.7 ± 41.4 pg/mL, AE-PCOS, control, P = 0.04) at BSL but was unaffected by intervention. Serum angiotensin-converting enzyme was greater in AE-PCOS versus control (101.9 ± 93.4 vs. 38.2 ± 14.7 pg/mL, P = 0.04) and reduced by ANT in AE-PCOS (77.7 ± 76.5 vs. 43.4 ± 27.3 µg/L, ANT, and ANT + T, P = 0.04) with no impact on control. Obese, IR women with AE-PCOS showed decreased integrated baroreflex gain and increased RAS activation compared with control.NEW & NOTEWORTHY Here we present evidence for an important role of testosterone in baroreflex control of blood pressure and renal responses to baroreceptor unloading in women with a common, high-risk androgen excess polycystic ovary syndrome (AE-PCOS) phenotype. These data indicate a direct effect of testosterone on the vascular system of women with AE-PCOS independent of body mass index (BMI) and insulin-resistant (IR). Our study indicates that hyperandrogenemia is a central underlining mechanism of heightened cardiovascular risk in women with PCOS.

Dexpanthenol protects against lipopolysaccharide-induced acute kidney injury by restoring AQP-2 levels via regulating SIRT-1 signaling pathway.

Acute kidney injury (AKI) is a serious pathology, causing dysfunction of urination and concentration due to damage to kidneys, resulting with blood pressure dysregulation and increased toxic metabolites. Dexpanthenol (DEX), a pantothenic acid analog, has anti-inflammatory and anti-apoptotic properties in various tissues. This study aimed to investigate the protective effects of DEX in systemic inflammation induced AKI. Thirty-two female rats were randomly assigned as control, lipopolysaccharide (LPS), LPS+DEX and DEX groups. LPS (5 mg/kg, single dose on 3rd day, 6 hours before sacrification) and DEX (500 mg/kg/d for 3 days) were administered intraperitoneally. After sacrification, blood samples and kidney tissues were collected. Hematoxylin-eosin, caspase-3 (Cas-3) and tumor necrosis factor alpha (TNF-α) staining were performed on kidney tissues. Total oxidant status (TOS) and total antioxidant status levels were measured with spectrophotometric method. Aquaporin-2 (AQP-2), silent information regulator gene-1 (SIRT1) and interleukin-6 (IL-6) gene expressions were detected with qRT-PCR. In the histopathological analysis, it was observed that DEX ameliorated histopathological changes. In the LPS group, there was an increase in blood urea nitrogen, creatinine, urea, TOS, oxidative stress index, IL-6, Cas-3, and TNF-α levels compared to the control group, while AQP-2 and SIRT1 levels were decreased. However, treatment with DEX reversed all these changes. In conclusion, DEX was found to be effective in preventing inflammation, oxidative stress, and apoptosis in the kidney through the SIRT1 signaling pathway. Thus, the protective properties of DEX suggest that it may be a potential therapeutic agent for kidney pathologies.

Item Banks for Measuring the Effect of Blood Pressure Dysregulation on Health-Related Quality of Life in Persons With Spinal Cord Injury

ObjectiveTo report on the development and calibration of the new Blood Pressure Dysregulation Measurement System (BPD-MS) item banks that assess the effect of BPD on health-related quality of life (HRQOL) and the daily activities of Veterans and non-Veterans with spinal cord injury (SCI). DesignCross-sectional survey study. SettingTwo Veteran Affairs medical centers and a SCI model system site. Participants454 respondents with SCI (n=262 American Veterans and n=192 non-Veterans; N=454). InterventionsNot applicable Main Outcome MeasuresThe BPD-MS item banks. ResultsBPD item pools were developed and refined using literature reviews, qualitative data from focus groups, and cognitive debriefing of persons with SCI and professional caregivers. The item banks then underwent expert review, reading level assessment, and translatability review prior to field testing. The items pools consisted of 180 unique questions (items). Exploratory and confirmatory factor analyses, item response theory modeling, and differential item function investigations resulted in item banks that included a total of 150 items: 75 describing the effect of autonomic dysreflexia on HRQOL, 55 describing the effect of low blood pressure (LBP) on HRQOL, and 20 describing the effect of LBP on daily activities. In addition, 10-item short forms were constructed based on item response theory-derived item information values and the clinical relevance of item content. ConclusionsThe new BPD-MS item banks and corresponding 10-item short forms were developed using established rigorous measurement development standards, which represents the first BPD-specific patient-reported outcomes measurement system unique for use in the SCI population.

Abstract #1402838: Thyroid Stimulating Hormone-Secreting Adenoma: A Rare Case of Hyperthyroidism

TSH-secreting adenomas account for only 0.5 to 3 % of all functioning pituitary tumors. We present this case report to highlight the importance of early diagnosis and prevention of severe complications. A 48-year-old postmenopausal female with a history of hypothyroidism was referred to our clinic for a second opinion. The patient had been stable on levothyroxine for over 10 years. Routine blood work was significant for elevated TSH and free T4. Despite adjustments to her levothyroxine, TSH and free T4 remained elevated. Her prior endocrinologist discontinued the levothyroxine and ordered an MRI brain, which showed an 8mm pituitary adenoma. The patient was referred to a neurosurgeon for evaluation, which then prompted the second endocrinology evaluation. Patient denied any palpitations, weight loss, heat intolerance, headaches, vision changes, or galactorrhea. Lab work repeated off of thyroid supplementation showed persistent elevated TSH at 6.5 mIU/L and free T4 at 2.1 ng/dL. Differential diagnosis included thyroid hormone resistance versus interference to thyroid assays versus TSHoma. The patient tested negative for the thyroid hormone resistance beta mutation, deeming thyroid hormone resistance unlikely. She tested negative for the human anti-mouse antibody, making interference to thyroid assays unlikely. Her alpha subunit level was normal, after which TSHoma was not a certainty. Since the diagnosis was unclear, patient was advised to follow up closely. Repeat MRI showed the tumor was now 1.2cm. Due to the increase in size, she was advised to proceed with trans-sphenoidal surgery (TSS). Pathology stained for TSH, confirming it was a TSH-secreting adenoma. After TSS, TSH normalized and free T4 was low, requiring the patient to be restarted on levothyroxine. TSH-secreting adenomas are quite rare, accounting for less than 1% of all cases of hyperthyroidism. Common clinical features include goiter, visual field defects, headache, menstrual disturbances, and galactorrhea. The presence of high free T4 and T3 and measurable serum TSH in the presence of a macroadenoma on MRI present strong evidence of a TSHoma. Definitive therapy includes transsphenoidal resection. Long-acting somatostatin analogs or dopamine agonists are used to restore euthyroidism prior to surgery. Long-term antithyroid drug therapy or thyroid ablation is not recommended because prolonged decreases in thyroid hormone secretion can stimulate TSH secretion and tumor growth. If TSHomas are left untreated, they can grow aggressively and impinge on nearby structures. Complications include visual field defects due to optic nerve compression, galactorrhea due to pituitary stalk compression, hypopituitarism leading to blood pressure dysregulation and decreased sexual function, and cardiac arrythmias leading to blood clots, stroke, and heart failure. Therefore, when hyperthyroxinemia is present with an elevated TSH, TSHoma should be considered. Even when alpha subunit levels are low or normal, TSHoma is still a possibility. Further investigation and close monitoring should be done to confirm diagnosis and prevent negative outcomes.