SBP Response Research Articles

Clinical response scores to predict blood pressure and renal function improvement following renal artery stenting for atherosclerotic renal artery stenosis

Abstract Background It is little known about predictors of systolic (SBP) and diastolic (DBP) blood pressure or renal function (eGFR) improvement in patients with atherosclerotic renal artery stenosis (ARAS) undergoing stent-assisted angioplasty (PTA). Therefore, we aimed to build a prediction scores that would indicate characteristics of patient subsets with ARAS most likely to have clinical improvement following PTA. Methods 201 patients who underwent PTA for ARAS (2003–2018) were categorized as eGFR or SBP/DBP responders based on eGFR increase of ≥11 ml/min/1.73m2, decrease of SBP ≥20mmHg and DBP ≥5mmHg at 12-months following PTA. The remaining patients were classified as non-responders. The performance of logistic regression models were evaluated by basic decision characteristics. Continuous data have been transformed into binary coding with help of operating characteristic (ROC) curve. Predictive models have been constructed for each followed by construction of predictive models in each of 3 categories. Results Logistic regression analysis showed that: baseline SBP>145 mmHg, DBP >82 mmHg, previous myocardial infarction and Renal-Aotric-Ratio >5.1 were independent influencing factors of SBP response, with relative risk percentage shares of 69.8%; 12.1%; 10.9%; and 7.2%, respectively (sensitivity: 82%, specificity: 86.3%, positive (PPV):82% and negative (NPV) predictive values: 86.3%). The DBP decrease prediction model included baseline SBP >145 mmHg and DBP >82 mmHg, the ARAS progression, index kidney length >106 mm, and bilateral PTA with respective shares of 35.0%; 21.8%; 18.2%; 13.3% and 11.8%. (sensitivity: 76%, specificity: 77.8%, PPV: 80.7% and NPV: 72.6%). The eGFR increase was associated with baseline serum creatinine >122 μmol/L but eGFR greater than 30 ml/min/1.73m2, index kidney length >98 mm, end-diastolic velocity in index renal artery, renal resistive index <0.74, and requirement for >3 BP medications, with respective shares of 24.4%; 24.4%; 21.2%; 15% and 15% (sensitivity: 33.3%, specificity: 93.5%, PPV: 65.6% and NPV: 78.9%). Conclusions Current study identified clinical characteristics of patients who most likely to respond to PTA for ARAS. The sutability of the score should be verified in a prospective cohort of patients referred to PTA of ARAS Funding Acknowledgement Type of funding source: None

Characterization of resting and exercise inter-arm differences in SBP to isometric handgrip exercise in males and females.

To characterize the eIAD response to IHE in males and females. On visit 1, participants (16 females and 15 males, aged 18-35 years) completed three maximal voluntary isometric contractions (MVIC) per arm. On visit 2, before IHE, a series of three simultaneous, bilateral BP measures were averaged at rest. During IHE, participants maintained handgrip at 20% of MVIC for 2 minutes (arm randomly assigned), at which time bilateral BP was measured (IHE) during exercise and subsequent recovery (REC1 and REC2). Repeated-measures analysis of variance assessed eIAD and SBP (time × sex). IHE increased absolute eIAD (4 mmHg). Differences in relative eIAD were observed at IHE and REC2 based on resting IAD status (P < 0.05). Females only had an exaggerated SBP and pulse pressure response in the working arm. Acute IHE was shown to augment eIAD. Further eIAD and resting IAD were related. Acute IHE induced different bilateral responses between males and females, though the impact of sex on eIAD warrants further investigation. Future studies should address the effects of repeated bouts of IHE, which may benefit individuals with a large resting IAD.

Association of plasma cyclooxygenase-2 levels and genetic polymorphisms with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults.

Cyclooxygenase (COX)-2, an inducible isoform of the major rate-limiting enzymes that regulate the production of prostaglandins is associated with injury, inflammation and proliferation. We sought to examine whether plasma COX-2 levels and its genetic variants is associated with salt sensitivity, BP changes and/or hypertension in humans. Eighty participants (aged 18-65 years) were maintained sequentially either on a usual diet for 3 days, a low-salt diet (3.0 g) for 7 days, and a high-salt diet (18.0 g) for an additional 7 days. In addition, we studied participants of the original Baoji Salt-Sensitive Study, recruited from 124 families from seven Chinese villages in 2004 who received the same salt intake intervention, and evaluated them for the development of hypertension. Plasma COX-2 levels were significantly decreased with reduction of salt intake from the usual to a low-salt diet and decreased further when converting from the low-salt to the high-salt diet. SNPs rs12042763 in the COX-2 gene was significantly associated with SBP responses to both low-salt and high-salt diet. SNPs rs689466 and rs12042763 were significantly associated with longitudinal changes in BPs. In addition, several COX-2 SNPs were significantly associated with incident hypertension over an 8-year follow-up. Gene-based analyses also supported the overall association of COX-2 with longitudinal changes in SBP and hypertension incidence. This study shows that dietary salt intake affects plasma COX-2 levels and that COX-2 may play a role in salt sensitivity, BP progression and development of hypertension in the Chinese populations studied.

Observations of the Exercise-Induced Interarm Blood Pressure Difference

ABSTRACT Blood pressure (BP) is used to aid in appropriate clinical decision making and monitor safe exercise participation. A large interarm difference (IAD) in systolic BP (≥10 mm Hg between arms; IAD+) at rest is associated with premature morbidity and mortality. Moderate-intensity aerobic exercise is known to influence IAD. Purpose The aims of the present study were to examine the relationship between resting IAD and exercise IAD (eIAD), and to characterize eIAD during a prolonged steady-state bout of aerobic exercise in IAD− (&lt;10 mm Hg between arms at rest) and IAD+ individuals. Methods Sixty-two participants were studied on two separate occasions. On the initial visit, anthropometric measures and a V˙O2peak test were completed. On the subsequent visit, participants cycled at 50% V˙O2peak for 30 min. Heart rate and sequential bilateral BP were measured at rest; at 5, 10, 20, and 30 min of exercise; and during active recovery. Descriptive statistics are reported as mean and SEM. The value of eIAD in predicting IAD was determined using multiple linear regression analysis. Absolute values and the percent (%) change in eIAD, systolic BP (right and left arms), and heart rate during exercise were examined between both IAD− and IAD+ individuals using a repeated-measures ANOVA. Results The incidence of IAD+ at rest was 19%. Twenty-five percent of the variation in resting IAD was predicted by eIAD (P &lt; 0.05). There were significantly different absolute and relative eIAD, and SBP responses to exercise between IAD+ and IAD−. Conclusion There is a relationship between eIAD and resting IAD that warrants further attention. The eIAD response is inherently different between IAD− and IAD+ individuals. It may be important to measure BP bilaterally during aerobic exercise.

6075Workload adjusted blood pressure response rather than peak systolic blood pressure is associated with increased all-cause mortality in males; results from 7097 treadmill exercise tests

Abstract Background Systolic blood pressure (SBP) is routinely measured during exercise testing (ET) and is in part determined by cardiac output and peripheral vascular resistance. A frequently used threshold for defining hypertensive response to exercise is ≥210 mmHg but this does not account for the fact that SBP is related to workload, via cardiac output. Purpose To examine the prognostic implications of considering external workload (METs) adjusted SBP response to exercise. Methods We reviewed all symptom-limited treadmill ET in males between 1987 and 2007 at a single centre (inclusion/exclusion criteria detailed in figure 1A). SBP was measured standing at rest and at peak exercise. Workload adjusted BP response with exercise (SBP/MET slope) was calculated as ΔSBP/ΔMET. METs were calculated from peak speed and grade according to the standard American College of Sports Medicine (ACSM) formula. Age-predicted peak METs was calculated as: 18 - 0.15 × age. Ten-year Cox proportional hazard ratios (HR) with 95% confidence intervals were calculated and adjusted as outlined in figure 1B. Results 7097 subjects were included, of which 1559 (22%) died within 10 years. Survivors were younger (57.2±10.6 y vs. 64.5±10.3 y, p&lt;0.001) and reached higher % of age-predicted METs (97±33% vs. 82±33%, p&lt;0.001). Survivors had higher peak SBP (181±26 vs. 176±27 mmHg, p&lt;0.001) as well as greater ΔSBP (49±22 vs. 42±22 mmHg, p&lt;0.001), while they had lower SBP/MET slope (7.0±4.4 vs. 8.9±6.5 mmHg/MET, p&lt;0.001). A peak SBP ≥210 mmHg was associated with better survival; 10-yr adjusted HR: 0.76 (0.64–0.88, p&lt;0.001). In contrast, a higher SBP/MET slope was associated with increased mortality (table 1). Table 1. Ten year adjusted hazard ratios Variable HR (95% CI) P Variable HR (95% CI) P Variable HR (95% CI) P Peak SBP, Q1: 100–159 mmHg REF REF Delta SBP, Q1: 1–29 mmHg REF REF SBP/MET slope, Q1: 0.2–4.2 REF REF Peak SBP, Q2: 160–179 mmHg 0.81 (0.71–0.94) 0.006 Delta SBP, Q2: 30–46 mmHg 0.80 (0.70–0.91) 0.001 SBP/MET slope, Q2: 4.3–6.2 0.95 (0.81–1.12) 0.562 Peak SBP, Q3: 180–199 mmHg 0.68 (0.58–0.78) &lt;0.001 Delta SBP, Q3: 47–61 mmHg 0.76 (0.66–0.88) &lt;0.001 SBP/MET slope, Q3: 6.2–9.1 1.18 (1.01–1.37) 0.032 Peak SBP, Q4: ≥200 mmHg 0.60 (0.51–0.69) &lt;0.001 Delta SBP, Q4: ≥62 mmHg 0.59 (0.50–0.69) &lt;0.001 SBP/MET slope, Q4: ≥9.1 1.40 (1.22– 1.62) &lt;0.001 HR, hazard ratio (adjusted according to figure 1B); SBP, systolic blood pressure; MET, metabolic equivalent of task; Q1–Q4, quartiles (Q1 as reference). Figure 1 Conclusion Workload adjusted blood pressure response to exercise in contrast to peak BP response was associated with increased mortality in male patients referred for ET. Of note, reaching a BP of at least 210 mmHg (suggested to define a hypertensive response to exercise) was associated with a 24% reduction in all-cause mortality. Acknowledgement/Funding K Hedman was supported by post-doc. grants from the Fulbright Commission, the Swedish Society of Medicine, County Council of Östergötland, Sweden

P3566Ambulatory blood pressure response to riboflavin supplementation in adults with the C677T polymorphism in the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR)

Abstract Background Epidemiological evidence suggests that the C677T polymorphism in the folate metabolising enzyme MTHFR is associated with a 24–87% increased risk of hypertension. Riboflavin (a cofactor for MTHFR) can modify this phenotype, as demonstrated in a series of RCTs, at this centre. ABPM measures BP over 24hrs and provides a more reliable assessment of an individual's BP compared to clinic BP. Aim To investigate the effect of riboflavin supplementation on BP (by ABPM) in adults with the MTHFR 677TT genotype. Methods Adults (n=3462) were recruited and screened for the MTHFRTT genotype and those eligible (n=81), were stratified by baseline SBP and randomised to receive riboflavin (10mg/day/16weeks) or placebo. Riboflavin status was measured using the erythrocyte glutathione reductase activation coefficient (EGRac) assay and clinic and ABPM were measured in accordance with clinical guidelines. Results Mean 24hr, daytime and night-time SBP was 6mmHg higher (p&lt;0.05) in adults with the TT v CC genotype. BP response to riboflavin was strongly dependent on baseline BP. In participants with a baseline SBP≥125mmHg, riboflavin resulted in a significant BP lowering in daytime SBP (Table). Day-time SBP response to riboflavin Treatment Placebo P-value Age 48.6 (11.3) 47.8 (12.0) 0.823 Male n (%) 17 (73.9) 12 (46.2) 0.093 BMI 28.8 (3.8) 27.2 (3.1) 0.131 Riboflavin status (EGRac)† Pre 1.33 (1.28–1.38) 1.29 (1.24–1.34) Post 1.20 (1.14–1.25) 1.31 (1.25–1.36) &lt;0.001 Change −0.12 0.02 Daytime BP (mmHg)‡ Pre 137.1 (132.7–141.3) 134.7 (130.3–139.1) Post 133.0 (128.9–138.1) 134.8 (130.6–139.1) 0.036 Change −3.8 −0.2 ANCOVA, adjusting for sex. †Higher EGRac values indicate lower riboflavin status; ‡mean of participant daytime/awake hrs personalised for each participant. Conclusion This is the first study to show, using ABPM, that riboflavin supplementation, targeted at adults with the MTHFR 677TT genotype, results in significant lowering of mean, day and night BP. Given the frequency of this genotype worldwide (approximately 10%, but as high as 30% in some populations) these findings could offer a personalised approach for BP management in at-risk sub-populations. Acknowledgement/Funding This work was supported by DSM Nutritional Products, Ltd and Wellcome Trust-Wolfston Northern Ireland Clinical Research Facility are acknowledged

NEW INSIGHTS FOR STATISTICAL ANALYSIS OF BLOOD PRESSURE RESPONSE TO RESISTANCE TRAINING IN ELDERLY HYPERTENSIVE WOMEN

ABSTRACT The main goal was to present statistical procedures for a better data interpretation of responsiveness, explain how to deal with RTM effect, and describe how to determine clinically important changes in BP from significant real difference (SRD). Twenty-seven hypertensive elderly women were included, and RT consisted of a periodized linear model. The RT lasted 10 weeks, with two sessions performed per week. Responders were classified on the basis of SBP differences between time-points T1 (first 3 weeks) and T4 (weeks 9-10). Statistical analyses were performed using One-Way Repeated Measures ANOVA, an analysis of covariance (ANCOVA), the linear mixed model (LMM) was used in the present study, and SRD was also calculated. In conclusion, when one-way repeated measure ANOVA was conducted to determine whether there was a statistically significant difference in SBP levels over the course of 10-week RT, results showed a non-significant reduction of -2.24 mmHg, while classifying subjects by responsiveness provides a different perspective of the results. Furthermore, initial SBP was the more powerful predictor of post-exercise SBP response, as analyzed by the regression to the mean effect. Finally, the reductions of -2.24 mmHg was not statistically significant nor clinically meaningful, but fell within the measurement error of the SBP measurements.

Abstract P1104: The Infusion of the Soluble Prorenin Receptor Increases Blood Pressure in High-Fat Fed Male Mice

Obesity-related hypertension is a major public health concern. We recently demonstrated that plasma levels of the soluble form of the prorenin receptor (sPRR) were elevated in obesity. In the present study, we aimed to determine whether sPRR contributed to blood pressure (BP) elevation in the context of obesity. High-fat fed C57BL/6 male mice were infused with vehicle (Veh) or sPRR (sPRR, 30 μg/kg) via subcutaneously implanted osmotic minipump for 4 weeks. BP parameters were recorded using radiotelemetry devices (n=6/groups). Male mice infused with sPRR exhibited higher systolic blood pressure (SBP. Veh: 133±1 mmHg, sPRR: 141±2 mmHg, P&lt;0.05) and mean arterial pressure (MAP. Veh: 116±1 mmHg, sPRR: 124±2 mmHg, P&lt;0.05) and lower spontaneous baroreflex sensitivity (Veh: 3.8±1.2 ms/ mmHg, sPRR: 2.1±0.5 ms/ mmHg, P&lt;0.05) than mice infused with vehicle. To define mechanisms involved in BP elevation, mice were injected with an angiotensin-II type 1 receptor antagonist (losartan), a muscarinic receptor antagonist (atropine), a β-adrenergic antagonist (propranolol) and a ganglionic blocker (chlorisondamine). Losartan did not blunt sPRR-induced elevation in SBP. However, SBP response to angiotensin II was increased in mice infused with sPRR suggesting that AngII could potentiate sPRR-induced elevation in SBP. Chlorisondamine treatment exacerbated the decrease in mean arterial pressure in male mice infused with sPRR compared with vehicle (MAP. Veh: -21±1 mmHg, sPRR: -29±1 mmHg, P&lt;0.05). Overall, we demonstrated that sPRR increased SBP through an impairment of the baroreflex sensitivity and an increase in the sympathetic tone in high-fat fed C57BL/6 male mice.

Intravenous Dexmedetomidine Combined with Ultrasound-Guided Rectus Sheath Block for Open Gastrectomy: a Prospective Randomized Trial

PurposeTo compare the incidences of positive hemodynamic response (HR > 100 beats min−1 or SBP > 160 mmHg) during abdominal exploration and moderate pain after surgery, when using dexmedetomidine infusion and rectus sheath block. MethodsOne hundred patients undergoing open gastrectomy were randomized to receive rectus sheath block with ropivacaine (Group B, n = 25), initial loading dose of 0.6 μg kg−1 dexmedetomidine, followed by a continuous infusion of 0.2 μg kg−1 h−1 throughout surgery (Group D, n = 25), both rectus sheath block and dexmedetomidine (Group BD, n = 25), or neither rectus sheath block nor dexmedetomidine (Group C, n = 25). General anesthesia techniques were standardized. HR, SBP, and positive hemodynamic response at peritoneum incision (TPI), 5 min (TAE-5), 10 min (TAE-10), and 15 min (TAE-15) after the start of abdominal exploration, and incidences of moderate postoperative pain were recorded. ResultsPositive hemodynamic responses during abdominal exploration were more common in Groups B (82%) and C (74%) than in Groups D (14%) and BD (9%) (all P = 0.000). HR and SBP were lower in Groups D and BD, compared with those in Groups C and B (all P < 0.05). Compared with TPI, HR and SBP increased significantly in Groups B and C during abdominal exploration (all P < 0.05), but not in Group BD (except HR at TAE-15). The incidences of moderate pain in Groups B and BD were noticeably lower than in Groups C and D at 1 h, 2 h, and 6 h after surgery (all P < 0.0083). ConclusionDexmedetomidine infusion combined with rectus sheath block provided more hemodynamic stability during abdominal exploration and better analgesia after surgery.

Outcomes of minority patients with very severe hypertension (>220/>120 mmHg).

Acute severe hypertension is a common problem among inner-city ethnic minority populations. Nevertheless, the effects of currently employed treatment regimens on blood pressure have not been determined in a clinical practice setting. We determined the SBP responses to acute antihypertensive drug protocols and the 2-year natural history of patients presenting with severe hypertension. Retrospective cohort investigation in consecutive patients with SBP at least 220 mmHg and/or DBP at least 120 mmHg during 3-month enrollment in 2014 with 2-year follow-up. Primary outcomes were SBP versus time for the first 5 h of emergency treatment and 2-year follow-up including repeat visits, target organ events, and hospitalizations. One hundred and fifty-six unique patients met criteria with 69% Black; 34% Hispanic; 56% had previous visits for severe hypertension; 31% had preexisting target injury. Acute management: Acute antihypertensive regimens resulted in grossly unpredictable and often exaggerated effects on SBP. Treatment acutely reduced SBP to less than 140 mmHg in 30 of 159 patients. Clonidine reduced SBP to less than 140 mmHg in 19/61. Two-year follow-up: We observed 389 repeat visits for severe hypertension, 99 new target events, and 76 hospitalizations accounting for 620 hospital days. Acute treatment of severe hypertension produced unpredictable and potentially dangerous responses in SBP. Two-year follow-up demonstrated extraordinary rates of recurrent visits, target organ events, and hospitalizations. Our findings indicate a need to develop effective management strategies to lower blood pressure safely and to prevent long-term consequences. Our findings may apply to other hospitals caring for ethnic minority populations.

Blood pressure elevation response to radiofrequency energy delivery: one novel predictive marker to long-term success of renal denervation.

Previous studies showed that radiofrequency energy delivery of the renal artery could induce an immediate and substantial blood pressure (BP)-elevation response, which might be indicative of the increase in central sympathetic nervous activity. The current study was to investigate whether the presence of BP-elevation response to radiofrequency energy delivery can serve as a surrogate to predict BP reduction following renal artery sympathetic denervation (RDN). Data were collected on 67 patients undergoing RDN for drug-resistant hypertension. The BP-elevation response to radiofrequency application was defined as elevation of SBP by at least 10 mmHg during radiofrequency energy delivery. The extent of BP reduction at 1, 3, 6, 12 months after RDN were analyzed. Multivariable linear regression analysis of baseline and procedural characteristics was performed to identify the determinants of BP reduction after RDN. Ten patients (14.9%) were classified as nonresponders to radiofrequency delivery and showed significantly lower BP reduction compared with responders. The SBP reductions of radiofrequency delivery responders vs. nonresponders were 31.2 ± 8.6 vs. 11.4 ± 8.6 mmHg, 36.3 ± 10.0 vs. 14.6 ± 10.6 mmHg, 39.9 ± 9.9 vs. 15.2 ± 8.8 mmHg, and 40.0 ± 8.7/13.5 ± 5.8 mmHg (P < 0.001 for all) at 1, 3, 6, and 12 months, respectively. On multiple linear regression analysis, higher baseline office SBP, the presence of BP-elevation response to radiofrequency energy delivery, and especially larger number of BP-elevation response points, were independent predictors of SBP reduction at 6-month and 12-month follow-up. Baseline SBP and BP-elevation response during radiofrequency ablation, as well as larger positive response points to radiofrequency energy delivery could be an effective intraprocedural predictive markers to long-term procedural success of RDN.

Blood pressure response to maximal dynamic exercise testing in an athletic population.

Exaggerated blood pressure (BP) response to exercise testing has been linked to left ventricular hypertrophy and myocardial fibrosis in competitive athletes. Due to frequent training, athletes are particularly exposed to high BP levels, but data on the magnitude and distribution of BP response to exercise in athletic populations is scarce. Cycle ergometry was performed in 2419 healthy competitive adolescent, professional and master athletes (age 26 ± 12 years, range 9-74, 27% women, 84 disciplines) for preparticipation screening. Fulfilling both subjective and at least two out of three objective exhaustion criteria (maximal heart rate >85% predicted, lactate ≥7 mmol/l, rate of perceived exertion ≥17) was required. Echocardiography was also performed. Maximal workload was 305 ± 59 W (mean ± SD) in men and 218 ± 40 in women. SBP increased significantly (men, Δ80 ± 20; women, Δ67 ± 16 mmHg; P < 0.001) to 204 ± 22 (men) and 180 ± 17 mmHg (women). DBP changed minimally (men: Δ0 ± 9, women: Δ2 ± 8 mmHg). The upper normative limit of SBP in men was 247 [95% CI 245-249; women: 214 (212-216) mmHg]. ESC guidelines of upper limits of maximal SBP were exceeded in 43% in men (>210 mmHg) and 28% in women (>190 mmHg). SBP response was more pronounced in endurance athletes, whereas DBP was slightly higher in strength athletes. Among cardiac dimensions, the strongest association for maximal SBP was found for left ventricular mass (r = 0.489; P < 0.001). SBP response to exercise testing is markedly exaggerated particularly in male endurance athletes. The prognostic significance of these findings regarding long-term cardiovascular alterations requires further clarification.

Abstract 133: Endothelial-Specific Interference With PPARγ Increases the Susceptibility to Angiotensin II-Induced Endothelial Dysfunction in Adult Offspring Born from AVP-Infused Pregnancies

Mutations in the ligand-activated transcription factor PPARγ result in hypertension, and synthetic agonists of PPARγ reduce blood pressure. Previously we found that mice expressing dominant-negative (DN) PPARγ driven by an endothelium-specific promoter (E-DN) exhibit vascular dysfunction. Preeclampsia (PE) is a hypertensive disorder of pregnancy which carries cardiovascular risk to offspring. PE is also associated with vascular dysfunction. We hypothesized a role for endothelial PPARγ in the pathogenesis of PE and its sequelae. C57BL/6J dams were bred with E-DN sires, and symptoms of PE were induced by infusion of vasopressin (AVP, 24 ng/hr sc) throughout gestation. Phenotypes of PE were first assessed in pregnant dams and then in adult offspring. Compared to saline infusion (SAL), AVP elevated maternal blood pressure (SBP: 116±3 vs 107±3, p&lt;0.05) at gestational day (GD) 14-15 and urine protein (70±6 vs 27±4 mg/mL, p&lt;0.05) at GD17. Offspring were phenotyped in adulthood. Data were stratified to sex, genotype, and exposure to AVP or SAL. At 20 weeks of age, SBP and vasorelaxation responses to acetylcholine were similar in offspring exposed to PE compared to mice born from SAL pregnancies. Adult offspring were next exposed to a sub-pressor dose of Angiotensin II (ANG; 120ng/kg/hr) for 14 days. Adult male ANG-treated E-DN born to PE pregnancies, but not NT mice exhibited significant impairment in ACh-induced relaxation in carotid artery (% relaxation: 62±10 vs 86±11, p&lt;0.05). Adult female ANG-treated E-DN exposed to PE also exhibited a trend for impaired endothelial function compared to NT controls (% relaxation: 63±9 vs 72±10). Endothelial dysfunction in male ANG-treated E-DN born to PE pregnancies was attenuated by tempol (relaxation improved from 56±9% vs 81±12%, p&lt;0.05), indicative of oxidative stress, and by a Rho-kinase inhibitor (relaxation improved from 73±11% vs 89±12%, p&lt;0.05). This data suggests that interference with endothelial PPARγ in pups born from PE pregnancies increases the risk for endothelial dysfunction upon exposure to a cardiovascular stressor in adulthood. Thus, conditions which impair PPARγ activity, such as obesity and diabetes, may predispose adult offspring born from PE pregnancy to cardiovascular disease.

Romantic Relationship Satisfaction and Ambulatory Blood Pressure During Social Interactions: Specificity or Spillover Effects?

People in high-quality romantic relationships tend to have lower blood pressure (BP). People may experience lower BP specifically when interacting with romantic partners. This study parsed the effects of different types of social interactions on ambulatory BP (ABP) and tested whether romantic relationship satisfaction moderated these effects during interactions with partners in particular (specificity) or with others (spillover; e.g., friends, co-workers). Partnered participants (N = 594) were drawn from a larger study on BP and cardiovascular health (age = 46.5 ± 9.3; 57.4% female). Participants reported on romantic relationship satisfaction and completed 24-hr ABP monitoring. At each reading, participants reported whether they had a social interaction and with whom. Multilevel models accounted for nesting of data over time. Romantic relationship satisfaction significantly modified the effects of some social interactions on systolic and diastolic BP (SBP, DBP). Participants with high (+1 SD) relationship satisfaction had significantly lower SBP (-0.77 mmHg, p = .02) during partner interactions compared with no social interaction; low-satisfaction (-1 SD) participants had a nonsignificant 0.59 mmHg increase (p = .14). A similar pattern emerged for DBP. Relationship satisfaction also modified SBP response during friend interactions (elevated SBP for low-satisfaction participants) and DBP response during "other" interactions (elevated DBP for high-satisfaction participants). Participants with high levels of romantic relationship satisfaction experienced significantly lower BP during social interactions with their partner compared with situations without social interaction. Although there was some evidence for spillover to other types of relationships, effects were largely restricted to partner interactions.

Increment in Systolic Blood Pressure During Cold Pressure Test Is Associated with Baseline LF Power in Young Prehypertensive Men

The cold pressor test (CPT) is commonly used as a sympathoexcitatory maneuver to provoke an increment in arterial pressure and heart rate and to measure cardiovascular reactivity to stress. However, use of the CPT as a predictor test of future hypertension is still debatable. We investigated whether exaggerated blood pressure responsiveness to CPT is observed in young prehypertensive men and determined baseline HRV indices and autonomic nervous system contribution into the elevation of blood pressure.CPT was performed in 81 normotensive and 72 prehypertensive men enrolled from V.N. Karazin Kharkiv National University student population. All participants gave written informed consent. After 5 min resting stage subjects placed their right hand into ice‐cold water for 1 minute. ECG was continuously recorded and resting HRV indices were interpreted (CardioLab 2010). Blood pressure was measured at the end of each stage (Nissei WS‐1011). GLM one‐way MANOVA and MANCOVA with height and BMI were used to test for possible effects of prehypertension on heart rate (ΔHR) and blood pressure (ΔSBP and ΔDBP) responses. The stepwise multiple linear regression analysis was carried out to assess the relative importance of baseline LnLF (LnLFrest) and LnHF (LnHFrest) power in HR, SBP, and DBP increments, adjusted also for the presence of prehypertension, BMI, height, and two‐way interactions.In the current study, prehypertensive subjects did not demonstrate higher cardiovascular reactivity to CPT (Table 1). Moreover, normotensives had higher SBP response to CPT (Table 1). When height and BMI were taken into account this difference was even more significant (not shown). Previous studies have yielded inconsistent results with some showing higher and some showing the same and even lower blood pressure reactivity to CPT in prehypertensive subjects or in persons with family history of hypertension.The stepwise multiple regression analysis revealed that ΔSBP in prehypertensives and ΔDBP in all subjects were negatively associated with LnLFrest possibly indicating, according to our hypothesis, activity of the inhibitory interneurons projected to the presympathetic neurons in the rostral ventrolateral medulla. The central inhibition of sympathetic activity reduced the increment of SBP in subjects developing hypertension and controlled increment of DBP in all subjects (Table 2).It was shown that increments in both SBP and DBP were associated with ΔHR only in the prehypertensive subjects and in persons with increased BMI (Table 2). These findings may be partially explained by blunting of baroreceptor reflex sensitivity and/or resetting of the baroreceptor reflex to a higher control point.in prehypertensives and in subjects with increased BMI. The increments in SBP and DBP associated also with ΔHR in subjects with a high level of baseline parasympathetic activity as shown by the positive association between LnHFrest by ΔHR interaction and ΔSBP or ΔDBP (Table 2) possibly because high LnHFrest reduces HR and increases atrioventricular delay which may contribute to a ventricular filling.In conclusion, young prehypertensive subjects demonstrated lower SBP response to CPT than normotensives possibly due to their increment in SBP was associated with resting LnLF power, indicating according to our hypothesis, inhibition of the presympathetic medullary neurons; ΔSBP and ΔDBP were associated with ΔHR only in prehypertensives and in persons with high baseline parasympathetic activity.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract WP335: Left Ventricular Hypertrophy and Anti-hypertensive Use in Intracerebral Hemorrhage

Intro: Elevated SBP is common after ICH. Continuous infusions of IV antihypertensive agents are often utilized to quickly correct SBP requiring ICU level care. It is difficult to predict SBP response to these treatments and subsequent medication weaning strategies, as SBP elevation can be the result or etiology of ICH. Identifying patients with a history of uncontrolled hypertension may help tailor SBP treatment. Left ventricular hypertrophy (LVH) on echocardiogram (echo) is a tool to assess for uncontrolled hypertension. Hypothesis: ICH patients with LVH require longer times of continuous infusions of antihypertensive medications (labetalol/nicardipine) compared to those without LVH. Methods: Admission demographics, medical history, continuous infusions of anti-hypertensives, echo data, ICH characteristics and medical/surgical interventions were prospectively collected for primary-ICH patients between 2009-2015. Patients without admission echo were excluded. LVH presence was evaluated as a binary variable and intergroup differences were evaluated using Mann-Whitney U or Student’s t- test for continuous variables and χ2 or Fisher exact test for categorical variables. Association of LVH presence and total duration of labetalol/nicardipine (in hours) within 72 h of ICU admission was evaluated using linear regression analysis after adjusting for age, race, ICH score and surgical intervention. Results: 370 primary-ICH patients with admission echo were identified. Of these patients, 252 (68%) patients had LVH. ICH patients with LVH were significantly younger (64 vs 69yo), had higher prevalence of pre-morbid hypertension (84 vs 64%), and higher ED and NICU admission SBP (189 vs 174mmHg; 158 vs 147mmHg). No intergroup differences in ICH score, surgical interventions or standing oral anti-hypertensive medication use was seen. Linear regression revealed ICH patients with LVH had longer times on continuous anti-hypertensive infusions compared to those without (20 vs 10h; β=0.11; p=0.04) after adjusting for aforementioned covariates. Conclusions: Our findings suggest that ICH patients with LVH on echo present with elevated SBP that is difficult to control. Early identification of this group may allow for earlier, tailored treatments.

Extraversion and cardiovascular responses to recurrent social stress: Effect of stress intensity

The present study sought to establish whether the effects of extraversion on cardiovascular responses to recurrent social stress are contingent on stress intensity. A 2×5×1 mixed-factorial experiment was conducted, with social stress intensity as a between-subject variable, study phase as a within-subject variable, extraversion as a continuous independent variable, and cardiovascular parameter (HR, SBP, DBP, or RSA) as a dependent variable. Extraversion (NEO-FFI), subjective stress, and physiological stress were measured in 166 undergraduate students randomly assigned to undergo moderate (n=82) or high-intensity (n=84) social stress (a public speaking task with different levels of social evaluation). All participants underwent continuous physiological monitoring while facing two consecutive stress exposures distributed across five laboratory phases: baseline, stress exposure 1, post-stress 1, stress exposure 2, post-stress 2. Results indicated that under moderate-intensity social stress, participants higher on extraversion exhibited lesser HR reactivity to stress than participants lower on extraversion, while under high-intensity social stress, they exhibited greater HR, SBP, DBP and RSA reactivity. Under both moderate- and high-intensity social stress, participants higher on extraversion exhibited pronounced SBP and DBP response adaptation to repeated stress, and showed either better degree of HR recovery or greater amount of SBP and DBP recovery after stress. These findings suggest that individuals higher on extraversion exhibit physiological flexibility to cope with social challenges and benefit from adaptive cardiovascular responses.

Egg white-derived peptides prevent cardiovascular disorders induced by mercury in rats: Role of angiotensin-converting enzyme (ACE) and NADPH oxidase

The study aimed to investigate the effects of egg white hydrolysate (EWH) on vascular disorders induced by mercury (Hg). For this, male Wistar rats were treated for 60days: Untreated (saline, i.m.); Mercury (HgCl2, i.m., 1st dose 4.6μg/kg, subsequent doses 0.07μg/kg/day); Hydrolysate (EWH, gavage, 1g/kg/day); Hydrolysate-Mercury. Systolic (SBP) and diastolic (DBP) blood pressure measurement and vascular reactivity experiments in aorta were performed. We analyzed endothelial dependent and independent vasodilator responses and vasoconstrictor response to phenylephrine (Phe) in absence and presence of endothelium, a NOS inhibitor, a NADPH oxidase inhibitor, the superoxide dismutase, a non-selective COX inhibitor, a selective COX-2 inhibitor, an AT-1 receptors blocker. In situ superoxide anion production, SOD-1, NOX-4, p22phox, COX-2 and AT-1 mRNA levels and NOX-1 protein expression were performed in aorta while the determination of angiotensin converting enzyme (ACE) activity was measured in plasma. As results, EWH prevented the increase in SBP and Phe responses and the endothelial dysfunction elicited by Hg, which was related to decreased ACE activity and NOX activation by EWH and, subsequently, alleviated ROS production and improved NO bioavailability in aorta. In conclusion, EWH could be considered as alternative or complementary treatment tools for Hg-induced cardiovascular damage.

Abstract P151: Salt Sensitivity in Male and Female C57BL/6J Mice: Role of Renal Angiotensin and Dopamine Receptors and Sodium Transporters

To test if there is a sex difference in the salt sensitivity of C57Bl/6J mice, we studied blood pressure (BP), renal dopamine receptors, and sodium transporters in response to high salt diet (4% NaCl, 1 wk) and candesartan. Similar to males, the night-time systolic BP (SBP, telemetry, n=4) in females started to increase on day 1, peaked on day 2 (130±1 vs 117±1, mm Hg) and remained at high levels (126±1); the daytime SBP started to increase on day 2 that became significant on day 6 (124±1 vs 111±1). The high salt-diet induced-increase in SBP was prevented by candesartan (1 mg/kg, 1 wk, subcutaneously via osmotic mini-pump) (82±3 vs. 117±2 in males; 86±2 vs. 121±1 in females, under anesthesia, n=5/group). There were no sex differences in the SBP response to diet and candesartan, food and water intakes, urinary excretions of water and electrolytes, and serum concentrations of creatinine and electrolytes on high and normal salt diet. In females fed a high salt diet, candesartan increased renal D 1 R (151±12, immunoblotting, % of control, n=5/group) and D 5 R (156±5) but not D 2 R, D 3 R , or D 4 R protein expression, increased renal mRNA expression of D 1 R(160±17) but not D 5 R (real-time PCR), and decreased the renal protein expressions of sodium-hydrogen exchanger isoform 3 (36±6), sodium-potassium-2 chloride cotransporter (8±2), sodium-chloride cotransporter (30±3), and α (55±4), β (60±8) and γ (9±1) epithelial sodium channel, but not type 2 sodium phosphate cotransporter and α1Na + K + ATPase. Those changes were also seen in males except that renal D 1 R protein expression was not increased. Under normal salt intake, AT 1A R KO females (C57Bl/6J background) had increased renal protein expressions of D 1 R (152±8), D 5 R (131±6), and D 4 R (114±4), but not D 2 R and D 3 R; renal protein expressions of sodium-hydrogen exchanger isoform 3 (47±8), sodium-potassium-2 chloride cotransporter (52±11), and α (42±9) and γ (46±7) epithelial sodium channel were decreased. We conclude that the increase in BP caused by high salt diet and the effect of AT 1 R blockade on BP, renal dopamine receptors and sodium transporters are similar in male and female C57Bl/6J mice . The consequences of the sex-related differential regulation of D 1 R and D 5 R, in pathophysiology, other than BP, remain to be determined.

P320 Differences in adrenergic components of baroreflex response to Valsalva maneuver in patients with multiple sclerosis and healthy subjects

Objectives To evaluate differences in recently developed, non-standard adrenergic baroreflex sensitivity (BRS) indices between patients with multiple sclerosis (MS) and healthy controls (HC). Methods This retrospective analysis included 153 patients with MS and 20 healthy controls. Systolic blood pressure (sBP) responses during Valsalva maneuver (VM) were divided into three subtypes: balanced – type 1 (a sBP dip below baseline in late phase II (IIL) and recovery in phase IV), suppressed – type 2 (a non-dipping BP) and augmented – type 3 (a BP recovery in phase IIL) autonomic response. Alternative adrenergic component of BRS (BRSa1), and alpha- ( α -BRSa) and beta-adrenergic ( β -BRSa) components of adrenergic BRS were calculated and compared between the groups. For a subset of 103 MS patients, data on epinephrine, norepinephrine and dopamine immediately prior to performing Valsalva maneuver were available for analysis. Results There was no difference in the subtypes of sBP responses during VM between groups. Patients with MS had significantly higher α -BRSa compared to HC (6.36 ± 2.44 vs. 5.02 ± 2.14, p = 0.02). No differences were found for BRSa1 and β -BRSa. When we looked at differences in all three parameters depending on subtypes of sBP responses during VM, significant difference in α -BRSa was maintained only for the subtype 3 (7.27 ± 2.05 vs. 5.88 ± 2.09, p = 0.045). We found positive correlation between epinephrine and BRSa1 (rs 0.226, p = 0.04), negative correlation epinephrine and β -BRSa (rs −0.195, p = 0.050) and positive correlation between norepinephrine and α -BRSa (rs 0.228, p = 0.021). Discussion It has been suggested that new BRSa measurements may help differentiate normal physiologic variants from mild dysautonomia. Conclusion Healthy subjects and MS patients exhibit different alpha-adrenergic response to Valsalva maneuver. Significance A significant correlation between blood catecholamines and alfa and beta adrenergic response to Valsalva maneuver was observed.