Mechanisms of blood pressure variability-induced cardiac hypertrophy and dysfunction in mice with impaired baroreflex

2005 ◽  
Vol 288 (3) ◽  
pp. R767-R776 ◽  
Author(s):  
Peter Martinka ◽  
Jens Fielitz ◽  
Andreas Patzak ◽  
Vera Regitz-Zagrosek ◽  
Pontus B. Persson ◽  
...  

Enhanced blood pressure variability contributes to left ventricular hypertrophy and end-organ damage, even in the absence of hypertension. We hypothesized that the greater number of high-blood pressure episodes associated with enhanced blood pressure variability causes cardiac hypertrophy and dysfunction by activation of mechanosensitive and autocrine pathways. Normotensive mice were subjected to sinoaortic baroreceptor denervation (SAD) or sham surgery. Twelve weeks later, blood pressure variability was doubled in SAD compared with sham-operated mice. Blood pressure did not differ. Cardiac hypertrophy was reflected in greater heart/body weight ratios, larger myocyte cross-sectional areas, and greater left ventricular collagen deposition. Furthermore, left ventricular atrial and brain natriuretic peptide mRNA expression was greater in SAD than in sham-operated mice. SAD had higher left ventricular end-diastolic pressures and lower myocardial contractility indexes, indicating cardiac dysfunction. Cardiac protein content of phosphorylated p125 focal adhesion kinase (p125 FAK) and phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) was greater in SAD than in sham-operated mice, indicating activation of mechanosensitive pathways of cardiac hypertrophy. Furthermore, enhanced cardiac renin and transforming growth factor-β1 (TGFbeta1) protein content indicates activation of autocrine pathways of cardiac hypertrophy. Adrenal tyrosine hydroxylase protein content and the number of renin-positive glomeruli were not different, suggesting that sympathetic activation and the systemic renin-angiotensin system did not contribute to cardiac hypertrophy. In conclusion, more frequent blood pressure rises in subjects with high blood pressure variability activate mechanosensitive and autocrine pathways leading to cardiac hypertrophy and dysfunction even in the absence of hypertension.

2011 ◽  
Vol 89 (3) ◽  
pp. 197-205 ◽  
Author(s):  
Katarina Mackovicova ◽  
Andrea Gazova ◽  
Dana Kucerova ◽  
Beata Gajdacova ◽  
Jan Klimas ◽  
...  

Angiotensin II can induce cardiac hypertrophy by stimulating the release of growth factors. ACE inhibitors reduce angiotensin II levels and cardiac hypertrophy, but their effects on the healthy heart are largely unexplored. We hypothesized that ACE inhibition decreases left ventricular mass in normotensive animals and that this is associated with altered expression of cardiac fetal genes, growth factors, and endothelial nitric oxide synthase (eNOS). Wistar rats (n = 7 per group) were orally administered with enalapril twice daily for a total daily dose of 5 mg·kg–1·d–1 (ENAP5) or 15 mg·kg–1·d–1 (ENAP15) or vehicle. Systolic blood pressure was measured by the tail-cuff method. Left ventricular expression of cardiac myosin heavy chain-α (MYH6) and -β (MYH7), atrial natriuretic peptide (ANP), endothelin-1 (ET-1), transforming growth factor β-1 (TGFβ-1), cardiotrophin-1 (CT-1), and renal renin were examined by real-time PCR, and eNOS using Western blot. Blood pressure was decreased only in ENAP15 animals (p < 0.05 vs. Control), whereas left ventricular mass decreased after both doses of enalapril (p < 0.05 vs. Control). MYH7 and ANP were reduced in ENAP15, while no changes in ET-1, TGFβ-1, CT-1, and MYH6 mRNA or eNOS protein were observed. Renal renin dose-dependently increased after enalapril treatment. Enalapril significantly decreased left ventricular mass even after 1 week treatment in the normotensive rat. This was associated with a decreased expression of the fetal genes MYH7 and ANP, but not expression of ET-1, CT-1, or TGFβ-1.


2004 ◽  
Vol 286 (4) ◽  
pp. H1229-H1235 ◽  
Author(s):  
Ernesto A. Aiello ◽  
María C. Villa-Abrille ◽  
Eduardo M. Escudero ◽  
Enrique L. Portiansky ◽  
Néstor G. Pérez ◽  
...  

In our studies with spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar rats, we observed normotensive WKY rats with cardiac hypertrophy determined by a greater left ventricular (LV) mass (LVM)-to-body weight (BW) ratio (LVM/BW) than that of normotensive Wistar rats. Thus we compared the following parameters in SHR, WKY, and Wistar rats: LVM/BW, cell capacitance as index of total surface area of the myocytes, length, width, and cross-sectional area of cardiac myocytes, LV collagen volume fraction, and myocardial stiffness. The LVM/BW of WKY (2.41 ± 0.03 mg/g, n = 41) was intermediate between SHR (2.82 ± 0.04 mg/g, n = 47) and Wistar rats (1.98 ± 0.04 mg/g, n = 28). A positive correlation between blood pressure and LVM was found in SHR, whereas no such relationship was observed in WKY or Wistar rats. Cell capacitance and cross-sectional area were not significantly different in SHR and WKY rats; these values were significantly higher than those of Wistar rats. The cell length was smaller but the width was similar in WKY compared with SHR. Papillary muscles isolated from the LV of WKY and SHR were stiffer than those from Wistar rats. Consistently, a greater level of myocardial fibrosis was detected in WKY and SHR compared with Wistar rats. These findings demonstrate blood pressure-independent cardiac hypertrophy in normotensive WKY rats.


2020 ◽  
Author(s):  
LJ Goudswaard ◽  
S Harrison ◽  
D Van De Klee ◽  
N Chaturvedi ◽  
DA Lawlor ◽  
...  

AbstractGreater blood pressure variability (BP) and reduced night-time BP dipping are associated with cardiovascular disease independently of mean BP in adults. This study examines whether these associations are apparent in adolescents. A cross-sectional analysis was undertaken in 587 UK adolescents. We examined associations between measures of blood pressure dipping and variability (including standard deviation weighted for day/night (SDdn), average real variability (ARV) and variability independent of the mean (VIM)) with cardiac structure measures assessed by echocardiography: (1) left ventricular mass indexed to height2.7 (LVMi2.7), (2) relative wall thickness (RWT), (3) left atrial diameter indexed to height (LADi), and (4) left ventricular internal diameter in diastole (LVIDD)). Greater BP variability was associated with cardiac structures including higher RWT, which persisted after adjustment for mean BP. There was no evidence for an association between night-time dipping and cardiac structures. Measurement of BP variability might benefit cardiovascular risk assessment in adolescents.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mussa K. Nsanya ◽  
Philip Ayieko ◽  
Ramadhan Hashim ◽  
Ezekiel Mgema ◽  
Daniel Fitzgerald ◽  
...  

AbstractEstimates for prevalence of high blood pressure (BP) among adolescents in Africa vary widely and few studies, if any, have documented the results of the recommended stepwise BP screening. In this cross-sectional study in Tanzania, we aimed to estimate prevalence of sustained high BP in 3 public secondary schools using the American Academy of Pediatrics BP screening strategy. On Day 1, one screening automated office BP (AOBP) measurement (Step 1) was followed by two more AOBP measurements (Step 2). Repeat AOBP measurements were obtained after about one month on adolescents with high AOBP measurements on Day 1 (Step 3). Participants with sustained high BP underwent 24-h ambulatory BP monitoring (step 4). Of all 500 enrolled participants, the prevalence of high blood pressure at each step in the process was 36.6% (183), 25.6% (128), 10.2% (51), and 2.6%(13) respectively for Steps 1–4. All except 6 students completed all 4 steps of the BP screening algorithm as indicated. We conclude that diagnosis of hypertension in African adolescents should use multiple AOBP measurements over multiple days followed by 24-h ABPM. Screening for high BP in school settings appears to be feasible and could provide a platform for cardiovascular disease education and health promotion.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Raihan Kabir ◽  
Prithvi Sinha ◽  
Sumita Mishra ◽  
Obialunanma V Ebenebe ◽  
Nicole Taube ◽  
...  

Exposure to inorganic arsenic (iAS) through drinking water is well-associated with adverse cardiovascular outcomes, yet the mechanisms through which it induces these effects are not fully understood. Recent epidemiological findings highlight an association between iAS exposure and altered left ventricular geometry in both the presence and absence of hypertension. We therefore tested the hypothesis that iAS exposure has a bimodal impact on cardiac-intrinsic and hemodynamic mechanisms that together induce pathological remodeling of the myocardium. Adult male and female mice were exposed to an environmentally relevant dose of 615 μg/L NaAsO 2 for eight weeks. Males (n=9-10 mice/group) exhibited increased systolic blood pressure (115.1±3.0 vs. 106.0±2.3 mmHg, p=0.0350) via tail cuff photoplethysmography, left ventricular wall thickening (0.98±0.01 vs. 0.88±0.01 mm, p<0.0001) via transthoracic echocardiography, increased heart weight to tibia length (8.56±0.21 vs. 7.15±0.24 mg/mm; n=24 mice/group), and increased plasma atrial natriuretic peptide (47.85±12.0 vs. 15.14±3.73 pg/mL, p=0.0379) via enzyme immunoassay. Myocardial mRNA transcript levels (n=10 hearts/group) of Acta1 (1.36±0.18 vs. 0.73±0.11, p=0.0037), Myh7 (1.53±0.15 vs. 1.04±0.10, p=0.0138), and Nppa (2.40±0.29 vs. 1.02±0.07, p=0.0001) were increased, and Myh6 (0.92±0.17 vs. 1.14±0.23, p=0.0001) was decreased, evidencing pathological hypertrophy in the male heart. Female hearts, however, were largely protected at this eight-week timepoint as similar changes were not detected. Further investigation found that Rcan1 was upregulated (1.47±0.19 vs. 0.97±0.04, p=0.0161; n=10 hearts/group) in male hearts, suggesting that calcineurin-NFAT was activated. Interestingly, iAS was sufficient to activate NFAT (0.82±0.11 vs. 0.46±0.05, p=0.0214; n=8 wells/group) independent of blood pressure via luciferase assay. In conclusion, these results demonstrate for the first time that iAS may cause pathological cardiac hypertrophy not only by increasing hemodynamic load, but also by activating calcineurin-NFAT and inducing fetal gene expression in the male heart, thus providing novel mechanistic insight into the threat of iAS exposure to the cardiovascular system.


PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0206945 ◽  
Author(s):  
Junko Kuwabara ◽  
Koichiro Kuwahara ◽  
Yoshihiro Kuwabara ◽  
Shinji Yasuno ◽  
Yasuaki Nakagawa ◽  
...  

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