Anatomical and Physiological Aspects of Cardiovascular Function in Wistar—Kyoto and Spontaneously Hypertensive Rats at Birth

1982 ◽  
Vol 63 (s8) ◽  
pp. 383s-385s ◽  
Author(s):  
Sarah D. Gray
Keyword(s):  
Arterial Wall ◽  
Spontaneously Hypertensive Rat ◽  
Left Ventricular ◽  
Small Sample ◽  
Heart Weight ◽  
Spontaneously Hypertensive ◽  
Cell Layers ◽  
The Media ◽  
Wistar Kyoto ◽  
Genetically Determined

1. The present study was designated to determine whether there are any detectable differences in cardiovascular anatomy or physiology between Wistar-Kyoto (WKY) and spontaneously hypertensive rat (SHR) pups at birth. 2. It was found that mean arterial pressures were significantly higher, heart rates were slightly higher, and heart weight/body weight ratios were higher in SHR. 3. Vascular dimensions were determined in a small sample of those rats, and the data there also indicate hypertrophy to some degree: the ratio of wall thickness/lumen radius was higher in SHR, tangential wall tension and number of cell layers in the media were increased. 4. It is concluded that some of the concomitant features of hypertension, such as left ventricular wall hypertrophy and arterial wall hypertrophy, may be genetically determined to some extent in SHR.

Calcineurin inhibition normalizes β-adrenergic responsiveness in the spontaneously hypertensive rat

2007 ◽  
Vol 293 (5) ◽  
pp. H3122-H3129 ◽  
Author(s):  
Scott M. MacDonnell ◽  
Hajime Kubo ◽  
David M. Harris ◽  
Xiongwen Chen ◽  
Remus Berretta ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Cardiac Contractility ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Heart Weight ◽  
Adrenergic Stimulation ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Calcineurin Activity ◽  
Calcineurin Inhibition

Calcineurin, a Ca2+-regulated protein phosphatase, links myocardial Ca2+ signaling with hypertrophic gene transcription. Calcineurin abundance increases in pressure-overload hypertrophy and may reduce agonist-mediated phospholamban (PLB) phosphorylation to underlie blunted β-adrenergic receptor (β-AR) responsiveness in hypertension. This hypothesis was tested by measuring the effects of calcineurin inhibition on changes in cardiac contractility caused by β-adrenergic stimulation in spontaneously hypertensive rats (SHR). Female SHR (age: 7 mo) and age-matched female Wistar-Kyoto rats (WKY) were studied. Heart weight-to-body weight ratio ( P < 0.01) and systolic blood pressure ( P < 0.01) were greater in SHR compared with WKY and were associated with increased myocardial calcineurin mRNA (CnAβ) and activity ( P < 0.05). β-AR stimulation with isoproterenol (Iso) increased calcineurin activity ( P < 0.05) in both WKY and SHR hearts, and this activity was suppressed with cyclosporin A (CsA) treatment. In SHR, CsA improved left ventricular whole heart and isolated myocyte β-AR responsiveness by normalizing PLB phosphorylation at Ser16 and Thr17 ( P < 0.05). These CsA-induced, PLB-mediated effects were associated with an augmentation in cardiomyocyte peak Ca2+ and a reduced rate (time constant of isovolumic pressure relaxation, tau) and magnitude of diastolic Ca2+ during β-AR stimulation. In conclusion, CsA normalized the blunted β-AR responsiveness associated with hypertension, in part, by mitigating calcineurin activity while improving PLB phosphorylation and subsequent sarcoplasmic reticulum Ca2+ regulation.

Cardiomyocyte function associated with hyperactivity and/or hypertension in genetic models of LV hypertrophy

2006 ◽  
Vol 290 (1) ◽  
pp. H463-H473 ◽  
Author(s):  
Bradley M. Palmer ◽  
Zengyi Chen ◽  
Richard R. Lachapelle ◽  
Edith D. Hendley ◽  
Martin M. LeWinter
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Left Ventricular ◽  
Adult Males ◽  
Compensatory Response ◽  
Spontaneously Hypertensive ◽  
Hypertrophic Response ◽  
Rat Strain ◽  
Males And Females ◽  
Sarcomere Dynamics ◽  
Wistar Kyoto

We examined cardiomyocyte intracellular calcium ([Ca2+]i) dynamics and sarcomere shortening dynamics in genetic rat models of left ventricular (LV) hypertrophy associated with or without hypertension (HT) and with or without hyperactive (HA) behavior. Previous selective breeding of the spontaneously hypertensive rat (SHR) strain, which is HA and HT, with the Wistar-Kyoto (WKY) rat strain, which is not hyperactive (NA) and not hypertensive (NT), has led to two unique strains: the WKHA strain, selected for HA and NT, and the WKHT strain, selected for NA and HT. Cardiomyocytes were isolated from young adult males and females of each strain, paced at 2, 3, and 4 Hz in 1.2 mM external Ca2+ concentration at 37°C, and cardiomyocyte [Ca2+]i and sarcomere dynamics were recorded simultaneously. Under these conditions, LV cardiomyocyte systolic and diastolic [Ca2+]i dynamics and diastolic sarcomere dynamics in the WKHT were significantly enhanced compared with WKY controls, suggesting an underlying LV hypertrophic response that successfully compensated for HT in the absence of HA. LV cardiomyocyte [Ca2+]i dynamics in the WKHA and SHR were strikingly similar to each other and only slightly reduced compared with WKY. LV cardiomyocyte systolic and diastolic sarcomere dynamics, on the other hand, were significantly reduced in the SHR compare with WKHA and more so in male than in female SHR. We conclude from these data that HT alone is an insufficient descriptor of the cause of LV hypertrophy and diminished LV cardiomyocyte function in the SHR rat. These data further suggest that HA (augmented by male sex) in the SHR may interact with the HT state to initiate impaired cardiomyocyte function and thereby inhibit or undermine an otherwise compensatory response that may occur with HT in the absence of HA.

Immunoreactive atrial natriuretic peptide in neuronal and glial cells of spontaneously hypertensive rat brain

1990 ◽  
Vol 258 (1) ◽  
pp. C109-C114 ◽  
Author(s):  
M. K. Raizada ◽  
B. Kimura ◽  
M. I. Phillips
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Glial Cells ◽  
Spontaneously Hypertensive Rat ◽  
Culture Media ◽  
Spontaneously Hypertensive ◽  
Glial Cultures ◽  
The Media ◽  
Wistar Kyoto ◽  
Atrial Natriuretic

Neuronal and glial cultures from the hypothalamic-brain stem areas of 1-day-old normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rat brains stained positively with atrial natriuretic peptide (ANP)-specific antibodies. The endogenous levels of the ANP immunoreactivity in WKY neuronal and glial cultures were 17.0 +/- 2.2 and 14.3 +/- 2.7 pg/mg, respectively. Comparable neuronal and glial cultures from SH rat brains contained a 48 to 70% decrease in the endogenous ANP immunoreactivity levels. Culture media from both brain cell types also contained ANP immunoreactivity, the levels of which are significantly higher than those found in the cells. However, similar to endogenous levels, the media levels of immunoreactive ANP in SH neuronal and glial cultures were significantly reduced compared with WKY brain cultures. These observations demonstrate that endogenous ANP-like immunoreactivity is found in neuronal and glial cells and is released into the media. The levels of peptide are reduced in cultures of SH compared with WKY cultures, suggesting a genetically controlled difference between the hypertensive and normotensive rat strains long before hypertension develops.

Troponin I phosphorylation in spontaneously hypertensive rat heart: effect of beta-adrenergic stimulation

1997 ◽  
Vol 273 (3) ◽  
pp. H1440-H1451 ◽  
Author(s):  
B. K. McConnell ◽  
C. S. Moravec ◽  
I. Morano ◽  
M. Bond
Keyword(s):  
Troponin I ◽  
Ventricular Myocytes ◽  
Spontaneously Hypertensive Rat ◽  
Left Ventricular ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Spontaneously Hypertensive ◽  
Myosin Light Chain 2 ◽  
Wistar Kyoto ◽  
Phospholamban Phosphorylation

We compared baseline and protein kinase A (PKA)-dependent troponin I (TnI) phosphorylation in 32Pi-labeled left ventricular myocytes from hearts of 26-wk spontaneously hypertensive rats (SHR) and Wistar-Kyoto controls (WKY). TnI phosphorylation was normalized to myosin light chain 2 phosphorylation, which was invariant. There was no difference in baseline TnI phosphorylation in SHR and WKY, but stimulation with isoproterenol, norepinephrine plus prazosin, forskolin, chloroadenosine 3',5'-cyclic monophosphate, or 3-isobutyl-1-methylxanthine caused a greater increase in TnI phosphorylation in the SHR than in the WKY. This was observed both in the presence and absence of the phosphatase inhibitor calyculin A; thus the differences in TnI phosphorylation between SHR and WKY are not due to decreased phosphatase activity in the SHR. After stimulation of the beta-adrenergic pathway, phospholamban phosphorylation was not different in SHR and WKY, indicating that the observed differences may be specific for PKA phosphorylation of TnI. The increased PKA-dependent TnI phosphorylation in the SHR resulted in decreased Ca2+ sensitivity of actomyosin adenosinetriphosphatase activity as compared with the WKY. We conclude that increased PKA-dependent TnI phosphorylation in the SHR may contribute to the impaired response to sympathetic stimulation.

Relative systolic dysfunction in female spontaneously hypertensive rat myocardium

2007 ◽  
Vol 103 (1) ◽  
pp. 353-358 ◽  
Author(s):  
Brian F. Renna ◽  
Scott M. MacDonnell ◽  
Patricia O. Reger ◽  
Deborah L. Crabbe ◽  
Steven R. Houser ◽  
...  
Keyword(s):  
Exercise Training ◽  
Spontaneously Hypertensive Rat ◽  
Systolic Function ◽  
Isolated Heart ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Lv Function ◽  
Spontaneously Hypertensive ◽  
Heart Preparation ◽  
Wistar Kyoto

Hypertension and exercise independently induce left ventricular (LV) remodeling and alter LV function. The purpose of this study was to determine systolic and diastolic LV pressure-volume relationships (LV-PV) in spontaneously hypertensive rats (SHR) with and without LV hypertrophy, and to determine whether 6 mo of exercise training modified the LV-PV in SHR. Four-month-old female SHR ( n = 20), were assigned to a sedentary (SHR-SED) or treadmill-trained (SHR-TRD) group (∼60% peak O2 consumption, 5 days/wk, 6 mo), while age-matched female Wistar-Kyoto rats (WKY; n = 13) served as normotensive controls. The LV-PV was determined using a Langendorff isolated heart preparation at 4 (no hypertrophy: WKY, n = 5; SHR, n = 5) and 10 mo of age (hypertrophy: WKY, n = 8; SHR-SED, n = 8; SHR-TRD, n = 7). At 4 mo, the LV-PV in SHR was similar to that observed in WKY controls. However, at 10 mo of age, a rightward shift in the LV-PV occurred in SHR. Exercise training did not alter the extent of the shift in the LV-PV relative to SHR-SED. Relative systolic function, i.e., relative systolic elastance, was ∼50% lower in SHR than WKY at 10 mo of age ( P < 0.05). Doppler-derived LV filling parameters [early wave (E), atrial wave (A), and the E/A ratio] were similar between groups. LV capacitance was increased in SHR at 10 mo ( P < 0.05), whereas LV diastolic chamber stiffness was similar between groups at 10 mo. Hypertrophic remodeling at 10 mo of age in female SHR is manifest with relative systolic decompensation and normal LV diastolic function. Exercise training did not alter the LV-PV in SHR.

Depressor effect of diabetes in the spontaneously hypertensive rat: associated changes in heart performance

1986 ◽  
Vol 64 (9) ◽  
pp. 1177-1184 ◽  
Author(s):  
Robert L. Rodgers
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Systolic Arterial Pressure ◽  
Left Ventricular ◽  
Stroke Work ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Rat Hearts ◽  
Heart Size ◽  
Wistar Kyoto

Effects of streptozotocin-induced diabetes (8 weeks) on the performance of perfused hearts from spontaneously hypertensive (SH) rats were compared with effects on normotensive Wistar–Kyoto (WK) and Sprague–Dawley (SD) rat hearts. Diabetes markedly decreased systolic arterial pressure (SAP) of SH rats in vivo but did not affect SAP of either of the normotensive strains. Diabetes also reduced heart size of SH and normotensive rats and reversed absolute left ventricular hypertrophy (wall-to-lumen ratios and left-to-right ventricular weight ratios) of SH rats. Heart perfusion at the end of the 8-week period revealed that diabetes (i) reduced hydraulic work at high pressure loads and efficiency of contraction (work/μ.LO2 consumed) of SH rat hearts but not of WK or SD hearts, and (ii) depressed left ventricular pulse pressure development (LVPP) and contractility (LV + dP/dt) of SH hearts more extensively than it reduced these variables in either of the normotensive control groups. Effects of diabetes which were similar in hypertensive and normotensive hearts were reductions in stroke work at high volume loads and depressions in LV−dP/dt. Attendant hypothyroidism probably contributed to the reductions in SAP, heart size, LVPP, LV+ and −dP/dt, and stroke work but not to the decreased efficiency or reversal of hypertrophy of SH rat hearts. Malnutrition of SH rats, like hypothyroidism, also decreased heart size without reversing hypertrophy but had no effect on SAP and only reduced LV−dP/dt. The results show that diabetes reversed hypertrophy and selectively reduced contraction efficiency, contractility, and LVPP of SH hearts, but otherwise the effects of diabetes in hypertensive and normotensive rat strains were similar to each other. The possible contribution of hypothyroidism to the observed effects of diabetes in SH rats remains to be clarified.

scholarly journals Progression of myocardial remodeling and mechanical dysfunction in the spontaneously hypertensive rat

2012 ◽  
Vol 303 (11) ◽  
pp. H1353-H1365 ◽  
Author(s):  
Ian J. LeGrice ◽  
Adèle J. Pope ◽  
Gregory B. Sands ◽  
Gillian Whalley ◽  
Robert N. Doughty ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Systolic Function ◽  
Three Dimensional ◽  
Hypertensive Heart Disease ◽  
Left Ventricular ◽  
Morphological Data ◽  
Systemic Hypertension ◽  
Myocardial Remodeling ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

The progression of hypertensive heart disease (HHD) to heart failure (HF) is associated with myocardial remodeling. Corresponding changes in three-dimensional organization of cardiac extracellular matrix have not been quantified or related fully to the development of HF. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto controls were studied at 3, 12, 18, and 24 mo. Hemodynamic and morphological data, brain natriuretic peptide levels, and echocardiography demonstrate four distinct disease stages: systemic hypertension, diastolic dysfunction, early systolic failure, and decompensated HF. Passive left ventricular (LV) pressure-volume relationships were determined in vitro. Transmural specimens from the anterior LV free wall were imaged using extended-volume confocal microscopy, and three-dimensional myocardial architecture was quantified. In SHRs, LV compliance was reduced at 12 mo and increased progressively thereafter. However, it was less than in controls for filling pressures <10 mmHg and not significantly different at ≥10 mmHg. Myocyte cross section was enlarged, with increased variability from 12 mo, while collagen fraction increased progressively. Perimysial collagen fraction remained unchanged with age, although endomysial collagen increased from 12 mo. Perimysial collagen between adjacent muscle layers fused at 12 mo and continued to thicken subsequently, while muscle layers became more dispersed and disordered. We conclude that LV dilatation, which accompanies decompensated HF in this model of HHD, is not due to LV “softening.” While perimysial (and endomysial) collagen networks are substantially remodeled, they are not dissolved, as has been proposed. We argue that progressive disruption of the laminar organization of LV myocardium may contribute to impaired systolic function in HHD.

Angiotensin II-induced structural and functional alterations in spontaneously hypertensive rat kidney

1996 ◽  
Vol 270 (1) ◽  
pp. F229-F236 ◽  
Author(s):  
C. K. Kost ◽  
W. A. Herzer ◽  
P. Li ◽  
M. Notoya ◽  
V. Mizuhira ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Structural Changes ◽  
Spontaneously Hypertensive Rat ◽  
Rat Kidney ◽  
Structural Effects ◽  
Prolonged Administration ◽  
Spontaneously Hypertensive ◽  
The Media ◽  
Wistar Kyoto ◽  
Renal Vascular

The purpose of this study was to compare functional and structural changes in the kidneys of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats during prolonged administration of angiotensin II. Rats were pretreated with captopril, and the effects of exogenous angiotensin II (200 ng.kg-1.min-1 for 7–14 days sc) on renal hemodynamics and renal vascular structure were examined. Angiotensin II induced significant reductions of renal blood flow and glomerular filtration and increases of renal vascular resistance in SHR but not WKY. Furthermore, angiotensin II induced an increase of the media/lumen ratio in the interlobular arteries (0.33 +/- 0.02 to 0.56 +/- 0.02) and arcuate arteries (0.27 +/- 0.02 to 0.53 +/- 0.07) of SHR without significantly altering the media/lumen ratio in the interlobular arteries (0.34 +/- 0.03 to 0.34 +/- 0.02) and arcuate arteries (0.30 +/- 0.02 to 0.36 +/- 0.05) of WKY (two-factor analysis of variance, strain x treatment; P = 0.0002 for interlobular arteries and P = 0.0319 for arcuate arteries). Results from this study indicate that the SHR kidney is more responsive than the WKY kidney to the functional and structural effects of prolonged angiotensin II infusion.

Hypertrophy of stellate ganglion cells in hypertensive, but not hyperactive, rats

1991 ◽  
Vol 261 (4) ◽  
pp. R979-R984 ◽  
Author(s):  
D. Peruzzi ◽  
E. D. Hendley ◽  
C. J. Forehand
Keyword(s):  
Arterial Wall ◽  
Spontaneously Hypertensive Rat ◽  
Ganglion Cells ◽  
Stellate Ganglion ◽  
Target Area ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rat ◽  
Wistar Kyoto ◽  
Carotid Arterial

The dendritic complexity of peripheral autonomic neurons is positively matched with the size of the target they innervate, apparently by trophic interactions with the target (D. Purves, W. D. Snider, and J. T. Voyvodic. Nature Lond. 336: 123-128, 1988). We have asked whether the vascular hypertrophy associated with hypertension is accompanied by dendritic hypertrophy of sympathetic ganglion cells. To do this, we examined the morphology of stellate ganglion cells in the spontaneously hypertensive rat (SHR), its normotensive control Wistar-Kyoto rat (WKY), and two new strains derived from the SHR that independently express the hypertensive phenotype of the SHR (WKHT) and the behavioral hyperactivity present in the SHR (WKHA). Cells were examined by intracellular staining with horseradish peroxidase in in vitro preparations of the ganglia. Carotid arterial wall size was also examined. Significant hypertrophy of both the carotid arterial wall and stellate ganglion cell dendrites was observed in the two hypertensive strains (SHR and WKHT) but not in either of the normotensive strains (WKY and WKHA). This increased total dendritic length of stellate ganglion cells associated with hypertension provides a greater target area for preganglionic innervation that may result in hyperinnervation of these cells.

Is Arterial Media Hypertrophy in Spontaneously Hypertensive Rats a Consequence of or a Cause for Hypertension?

1980 ◽  
Vol 59 (s6) ◽  
pp. 331s-333s ◽  
Author(s):  
K. J. Henrichs ◽  
T.H. Unger ◽  
K. H. Berecek ◽  
D. Ganten
Keyword(s):  
Blood Pressure ◽  
High Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Structural Changes ◽  
Peripheral Resistance ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
The Media ◽  
Wistar Kyoto ◽  
Genetically Determined

1. The increased peripheral resistance observed in established hypertension has been attributed to structural changes in the resistance vessels, which are considered to be due mainly to medial hypertrophy. This study was undertaken to examine the possiblity that structural changes in the arterial bed are genetically determined and may be causative factors in the development of high blood pressure in the spontaneously hypertensive rat. 2. The wall dimensions of aorta, renal artery and intrarenal arteries down to a distended diameter of 35 μm were studied: (a) in 14-week-old spontaneously hypertensive rats; (b) in age- and sex-matched spontaneously hypertensive rats which had been treated with captopril for two generations and had been normotensive during their complete life span; (c) in normotensive Wistar-Kyoto control rats. 3. Cross-sectional areas of the media were increased in the hypertensive rats in comparison with ‘normotensive spontaneously hypertensive rats’ and Wistar-Kyoto rats. Increased numbers of smooth muscle cells were found in the major arteries of hypertensive animals. 4. These results indicate that hypertrophy of the media is a consequence of high blood pressure rather than a genetically determined pathogenetic factor for the development of hypertension in spontaneously hypertensive rats.

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