scholarly journals Angiotensin-(1–7) attenuates angiotensin II-induced cardiac remodeling associated with upregulation of dual-specificity phosphatase 1

2012 ◽  
Vol 302 (3) ◽  
pp. H801-H810 ◽  
Author(s):  
LaTronya T. McCollum ◽  
Patricia E. Gallagher ◽  
E. Ann Tallant

Chronic hypertension induces cardiac remodeling, including left ventricular hypertrophy and fibrosis, through a combination of both hemodynamic and humoral factors. In previous studies, we showed that the heptapeptide ANG-(1–7) prevented mitogen-stimulated growth of cardiac myocytes in vitro, through a reduction in the activity of the MAPKs ERK1 and ERK2. In this study, saline- or ANG II-infused rats were treated with ANG-(1–7) to determine whether the heptapeptide reduces myocyte hypertrophy in vivo and to identify the signaling pathways involved in the process. ANG II infusion into normotensive rats elevated systolic blood pressure >50 mmHg, in association with increased myocyte cross-sectional area, ventricular atrial natriuretic peptide mRNA, and ventricular brain natriuretric peptide mRNA. Although infusion with ANG-(1–7) had no effect on the ANG II-stimulated elevation in blood pressure, the heptapeptide hormone significantly reduced the ANG II-mediated increase in myocyte cross-sectional area, interstitial fibrosis, and natriuretic peptide mRNAs. ANG II increased phospho-ERK1 and phospho-ERK2, whereas cotreatment with ANG-(1–7) reduced the phosphorylation of both MAPKs. Neither ANG II nor ANG-(1–7) altered the ERK1/2 MAPK kinase MEK1/2. However, ANG-(1–7) infusion, with or without ANG II, increased the MAPK phosphatase dual-specificity phosphatase (DUSP)-1; in contrast, treatment with ANG II had no effect on DUSP-1, suggesting that ANG-(1–7) upregulates DUSP-1 to reduce ANG II-stimulated ERK activation. These results indicate that ANG-(1–7) attenuates cardiac remodeling associated with a chronic elevation in blood pressure and upregulation of a MAPK phosphatase and may be cardioprotective in patients with hypertension.

2002 ◽  
Vol 282 (5) ◽  
pp. H1697-H1702 ◽  
Author(s):  
Hui Di Wang ◽  
Douglas G. Johns ◽  
Shanqin Xu ◽  
Richard A. Cohen

Our purpose was to address the role of NAPDH oxidase-derived superoxide anion in the vascular response to ANG II. Blood pressure, aortic superoxide anion, 3-nitrotyrosine, and medial cross-sectional area were compared in wild-type mice and in mice that overexpress human superoxide dismutase (hSOD). The pressor response to ANG II was significantly less in hSOD mice. Superoxide anion levels were increased twofold in ANG II-treated wild-type mice but not in hSOD mice. 3-Nitrotyrosine increased in aortic endothelium and adventitia in wild-type but not hSOD mice. In contrast, aortic medial cross-sectional area increased 50% with ANG II in hSOD mice, comparable to wild-type mice. The lower pressor response to ANG II in the mice expressing hSOD is consistent with a pressor role of superoxide anion in wild-type mice, most likely because it reacts with nitric oxide. Despite preventing the increase in superoxide anion and 3-nitrotyrosine, the aortic hypertrophic response to ANG II in vivo was unaffected by hSOD.


2000 ◽  
Vol 278 (4) ◽  
pp. H1241-H1247 ◽  
Author(s):  
Ad W. van Gorp ◽  
Dorette S. Van Ingen Schenau ◽  
Arnold P. G. Hoeks ◽  
Harry A. J. Struijker Boudier ◽  
Jo G. R. de Mey ◽  
...  

In hypertension arterial wall properties do not necessarily depend on increased blood pressure alone. The present study investigates the relationship between the development of hypertension and thoracic aortic wall properties in 1.5-, 3-, and 6-mo-old spontaneously hypertensive rats (SHR); Wistar-Kyoto rats (WKY) served as controls. During ketamine-xylazine anesthesia, compliance and distensibility were assessed by means of a noninvasive ultrasound technique combined with invasive blood pressure measurements. Morphometric measurements provided in vivo media cross-sectional area and thickness, allowing the calculation of the incremental elastic modulus. Extracellular matrix protein contents were determined as well. Blood pressure was not significantly different in 1.5-mo-old SHR and WKY, but compliance and distensibility were significantly lower in SHR. Incremental elastic modulus was not significantly different between SHR and WKY at this age. Media thickness and media cross-sectional area were significantly larger in SHR than in WKY, but there was no consistent difference in collagen density and content between the strains. Blood pressure was significantly higher in 3- and 6-mo-old SHR than in WKY, and compliance was significantly lower in SHR. The findings in this study show that in SHR, in which hypertension develops over weeks, alterations in functional aortic wall properties precede the development of hypertension. The decrease in compliance and distensibility at a young age most likely results from media hypertrophy rather than a change in intrinsic elastic properties.


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.


2016 ◽  
Vol 94 (12) ◽  
pp. 1349-1355 ◽  
Author(s):  
Baoling Zhu ◽  
Kai Liu ◽  
Chengzhi Yang ◽  
Yuhui Qiao ◽  
Zijian Li

Cardiac remodeling is the pathological basis of various cardiovascular diseases. In this study, we found gender-related differences in β-adrenergic receptor (AR)-mediated pathological cardiac remodeling. Cardiac remodeling model was established by subcutaneous injection of isoprenaline (ISO) for 14 days. Heart rate (HR), mean arterial pressure (MAP), and echocardiography were obtained on 7th and 14th days during ISO administration. Myocardial cross-sectional area and the ratio of heart mass to tibia length (HM/TL) were detected to assess cardiac hypertrophy. Picro–Sirius red staining (picric acid + Sirius red F3B) was used to evaluate cardiac fibrosis. Myocardial capillary density was assessed by immunohistochemistry for von Willebrand factor. Further, real-time PCR was used to measure the expression of β1-AR and β2-AR. Results showed that ISO induced cardiac remodeling, the extent of which was different between female and male mice. The extent of increase in cardiac wall thickness, myocardial cross-sectional area, and collagen deposition in females was less than that in males. However, no gender-related difference was observed in HR, MAP, cardiac function, and myocardial capillary density. The distinctive decrease of β2-AR expression, rather than a decrease of β1-AR expression, seemed to result in gender-related differences in cardiac remodeling.


1994 ◽  
Vol 07 (03) ◽  
pp. 110-113 ◽  
Author(s):  
D. L. Holmberg ◽  
M. B. Hurtig ◽  
H. R. Sukhiani

SummaryDuring a triple pelvic osteotomy, rotation of the free acetabular segment causes the pubic remnant on the acetabulum to rotate into the pelvic canal. The resulting narrowing may cause complications by impingement on the organs within the pelvic canal. Triple pelvic osteotomies were performed on ten cadaver pelves with pubic remnants equal to 0, 25, and 50% of the hemi-pubic length and angles of acetabular rotation of 20, 30, and 40 degrees. All combinations of pubic remnant lengths and angles of acetabular rotation caused a significant reduction in pelvic canal-width and cross-sectional area, when compared to the inact pelvis. Zero, 25, and 50% pubic remnants result in 15, 35, and 50% reductions in pelvic canal width respectively. Overrotation of the acetabulum should be avoided and the pubic remnant on the acetabular segment should be minimized to reduce postoperative complications due to pelvic canal narrowing.When performing triple pelvic osteotomies, the length of the pubic remnant on the acetabular segment and the angle of acetabular rotation both significantly narrow the pelvic canal. To reduce post-operative complications, due to narrowing of the pelvic canal, overrotation of the acetabulum should be avoided and the length of the pubic remnant should be minimized.


2020 ◽  
Vol 0 (4) ◽  
pp. 19-24
Author(s):  
I.M. UTYASHEV ◽  
◽  
A.A. AITBAEVA ◽  
A.A. YULMUKHAMETOV ◽  
◽  
...  

The paper presents solutions to the direct and inverse problems on longitudinal vibrations of a rod with a variable cross-sectional area. The law of variation of the cross-sectional area is modeled as an exponential function of a polynomial of degree n . The method for reconstructing this function is based on representing the fundamental system of solutions of the direct problem in the form of a Maclaurin series in the variables x and λ. Examples of solutions for various section functions and various boundary conditions are given. It is shown that to recover n unknown coefficients of a polynomial, n eigenvalues are required, and the solution is dual. An unambiguous solution was obtained only for the case of elastic fixation at one of the rod’s ends. The numerical estimation of the method error was made using input data noise. It is shown that the error in finding the variable crosssectional area is less than 1% with the error in the eigenvalues of longitudinal vibrations not exceeding 0.0001.


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