scholarly journals Early Spironolactone Treatment Attenuates Heart Failure Development by Improving Myocardial Function and Reducing Fibrosis in Spontaneously Hypertensive Rats

2015 ◽  
Vol 36 (4) ◽  
pp. 1453-1466 ◽  
Author(s):  
Marcelo D.M. Cezar ◽  
Ricardo L. Damatto ◽  
Luana U. Pagan ◽  
Aline R.R. Lima ◽  
Paula F. Martinez ◽  
...  
Keyword(s):  
Heart Failure ◽  
Spontaneously Hypertensive Rats ◽  
Type I Collagen ◽  
Myocardial Function ◽  
Type I ◽  
Hypertensive Rats ◽  
Collagen Concentration ◽  
Cross Sectional ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

Background: We evaluated the role of the aldosterone blocker spironolactone in attenuating long-term pressure overload-induced cardiac remodeling and heart failure (HF) in spontaneously hypertensive rats (SHR). Methods and Results: Thirteen month-old male SHR were assigned to control (SHR-C, n=20) or spironolactone (SHR-SPR, 20 mg/kg/day, n=24) groups for six months. Normotensive Wistar-Kyoto rats (WKY, n=15) were used as controls. Systolic blood pressure was higher in SHR groups and unchanged by spironolactone. Right ventricular hypertrophy, which characterizes HF in SHR, was less frequent in SHR-SPR than SHR-C. Echocardiographic parameters did not differ between SHR groups. Myocardial function was improved in SHR-SPR compared to SHR-C [developed tension: WKY 4.85±0.68; SHR-C 5.22±1.64; SHR-SPR 6.80±1.49 g/mm2; -dT/dt: WKY 18.0 (16.0-19.0); SHR-C 20.8 (18.4-25.1); SHR-SPR 28.9 (24.2-34.6) g/mm2/s]. Cardiomyocyte cross-sectional area and total collagen concentration (WKY 1.06±0.34; SHR-C 1.85±0.63; SHR-SPR 1.28±0.39 µg/mg wet tissue) were greater in SHR-C than WKY and SHR-SPR. Type 3 collagen expression was lower in SHR-C than WKY and unchanged by spironolactone. Soluble collagen, type I collagen, and lysyl oxidase did not differ between groups. Conclusion: Early spironolactone treatment decreases heart failure development frequency by improving myocardial systolic and diastolic function and attenuating hypertrophy and fibrosis in spontaneously hypertensive rats.

Distensibility of the Left Atrial Wall in Spontaneously Hypertensive Rats Compared with That in Normotensive Wistar-Kyoto Rats

1980 ◽  
Vol 59 (s6) ◽  
pp. 361s-363s
Author(s):  
S.-E. Ricksten ◽  
T. Yao ◽  
B. Ljung ◽  
P. Thorean
Keyword(s):  
Left Atrial ◽  
Spontaneously Hypertensive Rats ◽  
Relative Length ◽  
Hypertensive Rats ◽  
Atrial Wall ◽  
Cross Sectional ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Left Atrial Wall ◽  
Wistar Kyoto

1. The cardiac mechanoreceptors, which in rats are mainly located in the left atrial wall, are reset in spontaneously hypertensive rats. The atrial pressure has to be almost twice as high in spontaneously hypertensive rats as in normotensive controls to produce similar receptor activations, as is apparent from previous studies. 2. The present study was performed to investigate whether this resetting is due to decreased distensibility of left atrial walls in the spontaneously hypertensive rats. 3. Static load-length relationships were investigated in vitro on left atrial strips, and pressure-volume relationships were studied on isolated left atria from spontaneously hypertensive and normotensive Wistar-Kyoto rats. 4. The force per cross-sectional area exerted during a relative length increase of 80% was significantly greater in spontaneously hypertensive rats. The dynamic but not the static distensibility was significantly lower in these animals. 5. The decreased dynamic distensibility of left atrial walls in spontaneously hypertensive rats can at least partly explain the resetting of atrial receptor function.

scholarly journals Alteration of RhoA Prenylation Ameliorates Cardiac and Vascular Remodeling in Spontaneously Hypertensive Rats

2016 ◽  
Vol 39 (1) ◽  
pp. 229-241 ◽  
Author(s):  
Jian Yang ◽  
Yu-Ning Chen ◽  
Zao-Xian Xu ◽  
Yun Mou ◽  
Liang-Rong Zheng
Keyword(s):  
Cardiac Hypertrophy ◽  
Spontaneously Hypertensive Rats ◽  
Weight Ratio ◽  
Heart Weight ◽  
Farnesyl Pyrophosphate ◽  
Hypertensive Rats ◽  
Cross Sectional ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Aortic Remodeling

Background: In our previous study, farnesyl pyrophosphate synthase (FPPS) was shown to be increased in spontaneously hypertensive rats (SHR) and in mice with angiotensin-II induced cardiac hypertrophy. Overexpression of FPPS induced cardiac hypertrophy and fibrosis in mice, accompanied by an increase in the synthesis of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). In the present study, we investigated the mechanisms of reversing cardiovascular remodeling in SHR by inhibiting FPPS. Methods and Results: Six-week-old rats were given vehicle or an FPPS inhibitor (alendronate, 100 ug/kg/d) daily for twelve weeks by osmotic mini-pump. The results demonstrated that FPPS inhibition attenuated cardiac hypertrophy and fibrosis in SHR as shown by the heart weight to body weight ratio, echocardiographic parameters, and histological examination. In addition, FPPS inhibition attenuated aortic remodeling as shown by reduced media thickness, media cross-sectional area and collagen of the aorta as well as SBP, DBP, MBP. Furthermore, 12 weeks of alendronate treatment significantly decreased FPP and GGPP levels, RhoA activation and geranylgeranylation in the heart and aorta, all of which were significantly upregulated in SHR compared with normotensive Wistar-Kyoto rats. Conclusion: Taken together, these results indicate that chronic treatment with alendronate decreases the development of cardiac and aortic remodeling, by a pathway which involves inhibition of the geranylgeranylation and activation of RhoA.

scholarly journals Early rather than late aldosterone blockade improves myocardial function in spontaneously hypertensive rats without heart failure

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
MARCELO DIARCADIA MARIANO CEZAR ◽  
Silvio Junior ◽  
Paula Martinez ◽  
Ricardo Damatto ◽  
Aline Lima ◽  
...  
Keyword(s):  
Heart Failure ◽  
Spontaneously Hypertensive Rats ◽  
Myocardial Function ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Aldosterone Blockade

Impaired myocardial function in spontaneously hypertensive rats with heart failure

1991 ◽  
Vol 260 (1) ◽  
pp. H136-H145 ◽  
Author(s):  
C. H. Conrad ◽  
W. W. Brooks ◽  
K. G. Robinson ◽  
O. H. Bing
Keyword(s):  
Heart Failure ◽  
Muscle Function ◽  
Spontaneously Hypertensive Rats ◽  
Ventricular Hypertrophy ◽  
Myocardial Function ◽  
Left Ventricular ◽  
Hypertensive Rats ◽  
Shortening Velocity ◽  
Tension Development ◽  
Spontaneously Hypertensive

We have observed that many spontaneously hypertensive rats (SHR) between the ages of 18 and 24 mo develop findings suggestive of heart failure, including pleural and pericardial effusions, left atrial thrombi, and right ventricular hypertrophy. Isolated left ventricular papillary muscle function was studied in these animals (SHR-F), in age-matched SHRs without evidence of heart failure (SHR-NF), and in nonhypertensive controls (WKY). Preparations from SHR-F showed depression of active tension development (3.58 +/- 1.75 g/mm2, means +/- SD) compared with both SHR-NF (7.17 +/- 0.94) and WKY (6.17 +/- 1.00) (P less than 0.01). Shortening velocity was also depressed in SHR-F (0.95 +/- 0.38 lengths/s) compared with SHR-NF (1.60 +/- 0.30; P less than 0.05) and WKY groups (2.15 %/- 0.48; P less than 0.01). Depression of muscle function was not found before 18 mo of age. Thus the aging SHR is a model in which one can observe the transition from chronic stable left ventricular hypertrophy to overt heart failure. Furthermore, left ventricular papillary muscles from SHRs with heart failure show evidence of significant contractile dysfunction, suggesting that impairment of intrinsic myocardial function underlies the development of heart failure.

Excess oxygen delivery during muscle contractions in spontaneously hypertensive rats

1995 ◽  
Vol 78 (1) ◽  
pp. 101-111 ◽  
Author(s):  
J. M. Lash ◽  
H. G. Bohlen
Keyword(s):  
Blood Flow ◽  
Oxygen Saturation ◽  
Oxygen Delivery ◽  
Spontaneously Hypertensive Rats ◽  
Muscle Contractions ◽  
Hypertensive Rats ◽  
Hemoglobin Oxygen Saturation ◽  
Spontaneously Hypertensive ◽  
Tissue Po2 ◽  
Wistar Kyoto

These experiments determined whether a deficit in oxygen supply relative to demand could account for the sustained decrease in tissue PO2 observed during contractions of the spinotrapezius muscle in spontaneously hypertensive rats (SHR). Relative changes in blood flow were determined from measurements of vessel diameter and red blood cell velocity. Venular hemoglobin oxygen saturation measurements were performed by using in vivo spectrophotometric techniques. The relative dilation [times control (xCT)] of arteriolar vessels during contractions was as large or greater in SHR than in normotensive rats (Wistar-Kyoto), as were the increases in blood flow (2 Hz, 3.50 +/- 0.69 vs. 3.00 +/- 1.05 xCT; 4 Hz, 10.20 +/- 3.06 vs. 9.00 +/- 1.48 xCT; 8 Hz, 16.40 +/- 3.95 vs. 10.70 +/- 2.48 xCT). Venular hemoglobin oxygen saturation was lower in the resting muscle of SHR than of Wistar-Kyoto rats (31.0 +/= 3.0 vs. 43.0 +/- 1.9%) but was higher in SHR after 4- and 8-Hz contractions (4 Hz, 52.0 +/- 4.8 vs. 43.0 +/- 3.6%; 8 Hz, 51.0 +/- 4.6 vs. 41.0 +/- 3.6%). Therefore, an excess in oxygen delivery occurs relative to oxygen use during muscle contractions in SHR. The previous and current results can be reconciled by considering the possibility that oxygen exchange is limited in SHR by a decrease in anatomic or perfused capillary density, arteriovenular shunting of blood, or decreased transit time of red blood cells through exchange vessels.

scholarly journals Aging Additively Influences Insulin- and Insulin-Like Growth Factor-1-Mediated Endothelial Dysfunction and Antioxidant Deficiency in Spontaneously Hypertensive Rats

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 676
Author(s):  
Kunanya Masodsai ◽  
Yi-Yuan Lin ◽  
Sih-Yin Lin ◽  
Chia-Ting Su ◽  
Shin-Da Lee ◽  
...  
Keyword(s):  
Growth Factor ◽  
Endothelial Dysfunction ◽  
Spontaneously Hypertensive Rats ◽  
No Production ◽  
Organ Bath ◽  
Insulin Like Growth Factor ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Nos Inhibitors ◽  
Wistar Kyoto

This study aimed to investigate the aging-related endothelial dysfunction mediated by insulin and insulin-like growth factor-1 (IGF-1) and antioxidant deficiency in hypertension. Male spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar–Kyoto rats (WKYs) were randomly divided into 24-week-old (younger) and 48-week-old (older) groups, respectively. The endothelial function was evaluated by the insulin- and IGF-1-mediated vasorelaxation of aortic rings via the organ bath system. Serum levels of nitric oxide (NO), malondialdehyde (MDA), catalase, and total antioxidant capacity (TAC) were examined. The insulin- and IGF-1-mediated vasorelaxation was significantly impaired in both 24- and 48-week-old SHRs compared with age-matched WKYs and was significantly worse in the 48-week-old SHR than the 24-week-old SHR. After pretreatments of phosphoinositide 3-kinase (PI3K) or NO synthase (NOS) inhibitors, the insulin- and IGF-1-mediated vasorelaxation became similar among four groups. The serum level of MDA was significantly increased, while the NO, catalase, and TAC were significantly reduced in the 48-week-old SHR compared with the 24-week-old SHR. This study demonstrated that the process of aging additively affected insulin- and IGF-1-mediated endothelial dysfunction in SHRs, which could be partly attributed to the reduced NO production and antioxidant deficiency.

Sign in / Sign up

Export Citation Format

Share Document