Involvement of iNOS in postischemic heart dysfunction of stroke-prone spontaneously hypertensive rats

We investigated the possible contribution of inducible nitric oxide synthase (iNOS) to postischemic heart dysfunction and injuries in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP, 13–14 wk of age, had significantly higher systolic blood pressure and greater heart weight than age-matched Wistar-Kyoto rats (WKY). Permanent occlusion of the left anterior descending coronary artery (LAD) caused significant and long-lasting increases in the activity and mRNA expression of myocardial iNOS in SHRSP compared with WKY. However, there was no significant difference in the LAD occlusion-induced expression of interleukin-1β mRNA between SHRSP and WKY. Hemodynamic deterioration and myocardial fibrosis were also observed in SHRSP at 4 wk after LAD occlusion. Continuous administration of 2-amino-5,6-dihydro-6-methyl-4 H-1,2-thiazin (AMT) completely blocked the LAD occlusion-induced increase in the myocardial iNOS activity of SHRSP. Moreover, postischemic heart dysfunction and injuries were also significantly ameliorated by 2-amino-5,6-dihydro-6-methyl-4 H-1,2-thiazin (AMT). These results suggest that the increased activity of myocardial iNOS plays a pivotal role in the development of postischemic cardiac dysfunction and injuries in SHRSP with the hypertensive and hypertrophic heart.

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Sustained density of neuroendocrine cells with aging precedes development of prostatic hyperplasia in spontaneously hypertensive rats

BMC Urology ◽

10.1186/s12894-019-0528-7 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Yuki Kyoda ◽

Koji Ichihara ◽

Kohei Hashimoto ◽

Ko Kobayashi ◽

Fumimasa Fukuta ◽

...

Keyword(s):

Spontaneously Hypertensive Rats ◽

Prostatic Hyperplasia ◽

Neuroendocrine Cells ◽

Initial Growth ◽

Hypertensive Rats ◽

Initial Development ◽

Spontaneously Hypertensive ◽

Significant Difference ◽

The Difference ◽

Wistar Kyoto

Abstract Background Neuroendocrine (NE) cells may have an impact on the development and initial growth of benign prostatic hyperplasia (BPH) according to previous human studies. Methods To explore the relationship of NE cells and BPH development, we compared the density of NE cells and also prostatic weight in spontaneously hypertensive rats (SHR), which develop by aging, and Wistar-Kyoto rats (WKY) as control. The total weights of the epithelium and stroma in the ventral lobes of 8-, 12, 16-, 28- and 56-week-old SHR and WKY were calculated using Image J software. NE cells in the ventral prostatic ducts (VPd) were quantified using immunohistochemical staining for serotonin. Results Although there was no significant difference in the estimated total weight of the epithelium and stroma in the ventral lobes adjusted by body weight (ES weight) between the two groups at 8, 12 and 16 weeks of age, ES weight was significantly greater in the SHR group than in the WKT group at 28 and 56 weeks. The density of NE cells in the VPd decreased with aging in the WKY group, whereas it was sustained until 16 weeks and then decreased with aging in the SHR group. The difference in the density between the two groups was most marked at 16 weeks of age. Conclusion In the natural history of BPH, NE cells may play an important role in the initial development of BPH because sustained density of NE cells in the VPd precedes the development of prostatic hyperplasia.

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Interleukin-1βAccelerates the Onset of Stroke in Stroke-Prone Spontaneously Hypertensive Rats

Mediators of Inflammation ◽

10.1155/2012/701976 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 17

Author(s):

Tsuyoshi Chiba ◽

Tatsuki Itoh ◽

Masaki Tabuchi ◽

Toru Nakazawa ◽

Takao Satou

Keyword(s):

Spontaneously Hypertensive Rats ◽

Immune Cell ◽

Stroke Onset ◽

Blood Levels ◽

Hypertensive Rats ◽

Gene Expressions ◽

Continuous Administration ◽

Spontaneously Hypertensive ◽

Protein Levels ◽

Wistar Kyoto

High blood levels of inflammatory biomarkers and immune cells in stroke lesions have been recognized as results of stroke. However, recent studies have suggested that inflammation occurs prior to stroke onset. In this study, we aimed to clarify the role of inflammation in stroke onset among stroke-prone spontaneously hypertensive rats (SHRSP). At 4 weeks of age (before stroke onset), the plasma level of IL-1βwas significantly higher in SHRSP (153.0±49.7 pg/ml) than in Wistar Kyoto rats (WKY) (7.7±3.4 pg/ml,P<0.001versus SHRSP) or spontaneously hypertensive rats (SHR) (28.0±9.1 pg/ml,P<0.001versus SHRSP) (n=6per strain). Stimulated IL-1βsignal was also observed in cerebrovascular endothelial cells of SHRSP. Gene expressions of IL-1β, IL-1 receptors, caspase-1, and downstream genes (MCP-1 and ICAM-1), which associated with immune cell recruitment, were significantly greater in SHRSP than in WKY or SHR, coincident with greater NFκB protein levels in SHRSP compared to WKY or SHR. In addition, continuous administration of IL-1β(2 μg/day) using an osmotic pump slightly increased the incidence of stroke in SHR (P=0.046) and significantly accelerated the onset of stroke in SHRSP (P=0.006) compared to each control (n=10per group). These results suggest that a stimulated IL-1βsignal might be a cause of stroke onset when concomitant with severe hypertension.

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Intra-Erythrocyte Sodium and (Na+,K+-Activated)-ATPase Concentration and Urinary Aldosterone Excretion in Spontaneously Hypertensive Rats

Clinical Science ◽

10.1042/cs0600229 ◽

1981 ◽

Vol 60 (2) ◽

pp. 229-232 ◽

Cited By ~ 13

Author(s):

G. Berglund ◽

L. Sigström ◽

S. Lundin ◽

B. E. Karlberg ◽

H. Herlitz

Keyword(s):

Spontaneously Hypertensive Rats ◽

Sodium Concentration ◽

Intracellular Sodium ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Wistar Kyoto Rats ◽

Significant Difference ◽

Intracellular Sodium Concentration ◽

Erythrocyte Sodium ◽

Wistar Kyoto

1. Intra-erythrocyte sodium, potassium, ATP and (Na+,K+-activated)-ATPase concentrations and urinary aldosterone excretion were compared in 3-month-old spontaneously hypertensive rats (n = 11) and normotensive Wistar-Kyoto control rats (n = 11). 2. Spontaneously hypertensive rats exhibited significantly higher intra-erythrocyte sodium concentration (5.5 ± 1.3 vs 4.0 ± 1.1 mmol/l of erythrocytes, P < 0.01). No significant difference was found in intra-erythrocyte potassium, ATP or (Na+,K+-activated)-ATPase concentration. 3. Mean urinary aldosterone excretion was significantly lower in spontaneously hypertensive rats (66.3 ± 6.5 pmol/24 h) than in Wistar-Kyoto rats (90.5 ± 10.6 pmol/24 h, P < 0.01). No significant relationship between urinary aldosterone and intra-erythrocyte sodium concentration was found in spontaneously hypertensive or Wistar-Kyoto rats or in the pooled group. 4. These results are thus consistent with previous findings of an increased intracellular sodium concentration in spontaneously hypertensive rats, but do not support the hypothesis that aldosterone is a dominant regulator of intracellular sodium concentration.

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Cytoplasmic free [Ca2+] is not increased in the platelets of deoxycorticosterone–salt and spontaneously hypertensive rats

Clinical Science ◽

10.1042/cs0710121 ◽

1986 ◽

Vol 71 (1) ◽

pp. 121-123 ◽

Cited By ~ 14

Author(s):

Koh-Ichi Murakawa ◽

Yoshiharu Kanayama ◽

Masakazu Kohno ◽

Takahiko Kawarabayashi ◽

Kenichi Yasunari ◽

...

Keyword(s):

Spontaneously Hypertensive Rats ◽

Free Calcium ◽

Sprague Dawley ◽

Hypertensive Rats ◽

Acetoxymethyl Ester ◽

Spontaneously Hypertensive ◽

Sprague Dawley Rats ◽

Significant Difference ◽

Free Calcium Concentration ◽

Wistar Kyoto

1. The cytoplasmic free calcium concentration ([Ca2+]i) in the platelets of spontaneously hypertensive rats (SHR), Wistar–Kyoto rats (WKY), deoxycorticosterone–salt hypertensive rats (DOC) and normotensive Sprague–Dawley rats (SD) was measured with the fluorescent dye, quin-2-tetra-acetoxymethyl ester. 2. No significant difference in platelet [Ca2+]i was found between SHR and WKY or between DOC and SD rats. 3. No correlations were found between systolic blood pressure and [Ca2+]i. 4. These results suggest that the elevation of platelet [Ca2+]i does not necessarily accompany hypertension in rats.

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Vasorelaxation effect of Syzygium polyanthum (wight) walp. Leaves extract on isolated thoracic aorta rings of normal and hypertensive rats

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v15i1.1264 ◽

2016 ◽

Vol 15 (1) ◽

Author(s):

Azlini Ismail ◽

Wan Amir Nizam Wan Ahmad

Keyword(s):

Thoracic Aorta ◽

Spontaneously Hypertensive Rats ◽

Negative Control ◽

Distilled Water ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Traditional Remedy ◽

Ic50 Value ◽

Significant Difference ◽

Wistar Kyoto

Introduction: Syzygium polyanthum (Wight) Walp. leaves are traditionally consumed by the Malays as an alternative treatment for hypertension. Until now, effect of S. polyanthum leaves extract on blood vessel is not yet disclosed. Methods: This study investigated the effect of S. polyanthum leaves aqueous extract (AESP) (0.01, 0.1, 1 & 10 mg/ml) on isolated thoracic aorta rings of normotensive Wistar-Kyoto rats (WKY) and Spontaneously Hypertensive rats (SHR). Both rings were pre-contracted using phenylephrine (1 µM). Distilled water that dissolved AESP served as negative control. Results: As compared to negative control, AESP at 0.1, 1, and 10 mg/ml significantly relaxed aorta rings of WKY by 39.81 ± 2.99 % (P<0.001), 59.55 ± 7.60 % (P<0.001), and 72.58 ± 5.57 % (P<0.001), respectively. In SHR, AESP at 1 and 10 mg/ml significantly relaxed the aorta rings of SHR by 40.53 ± 3.66 % (P<0.001) and 65.73 ± 8.24 % (P<0.001), respectively. There was a significant difference between AESP-induced vasorelaxation in WKY and in SHR at a concentration of 0.1 mg/ml (P<0.001). The IC50 value for AESPinduced vasorelaxation on aorta rings of WKY (94.67 ± 1.41 µg/ml) was lower than of SHR (799.80 ± 1.69 µg/ml). Conclusions: The S. polyanthum leaves extract was able to cause significant relaxation on aorta rings of both normal and hypertensive rats. Thus, this finding is well-corroborated with the use of this plant as a traditional remedy for hypertension. It is suggested that an in-depth investigation of the mechanism of vasorelaxation of this plant is carried-out in the future.

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

Cellular Physiology and Biochemistry ◽

10.1159/000445619 ◽

2016 ◽

Vol 39 (1) ◽

pp. 229-241 ◽

Cited By ~ 7

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.

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Altered intracellular adrenoceptor distribution in myocardium of spontaneously hypertensive rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1987.253.4.h904 ◽

1987 ◽

Vol 253 (4) ◽

pp. H904-H908 ◽

Cited By ~ 2

Author(s):

C. J. Limas ◽

C. Limas

Keyword(s):

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Beta Agonists ◽

Significant Difference ◽

Beta Receptors ◽

Alpha Receptors ◽

Total Complement ◽

Membrane Bound ◽

Wistar Kyoto

The number of membrane-bound beta-adrenoceptors is reduced in the myocardium of spontaneously hypertensive rats, and this decline may account for the decreased inotropic responsiveness to beta-agonists. It is not known, however, whether the total complement of cellular beta-receptors is lower in hypertensive animals. This issue was examined using two different approaches: acid elution of cell surface-bound beta-receptor ligands and comparison of the number of receptors in the plasma membrane and a postcytosolic vesicular fraction. Approximately 30% of the total beta-receptors were located intracellularly in Wistar-Kyoto rats compared with 42% for spontaneously hypertensive rats. Similarly, a decline in membrane-bound beta-receptors in hypertensive rats was balanced by a rise in receptors associated with the vesicular fraction. In contrast, alpha 1-adrenoceptors were higher in the membrane and lower in the vesicular fraction of hypertensive rats without a significant difference in total alpha-receptors compared with normotensive animals. Differences in adrenergic responsiveness in this, and perhaps other, models of cardiac hypertrophy reflect altered intracellular distribution of adrenoceptors, which may be under the control of the sympathetic nervous system.

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Medullospinal sympathoexcitatory neurons in normotensive and spontaneously hypertensive rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1986.250.5.r910 ◽

1986 ◽

Vol 250 (5) ◽

pp. R910-R917 ◽

Cited By ~ 4

Author(s):

M. K. Sun ◽

P. G. Guyenet

Keyword(s):

Spontaneously Hypertensive Rats ◽

Discharge Rate ◽

Maximal Activity ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Wky Rats ◽

Significant Difference ◽

Wistar Kyoto ◽

The Relationship ◽

Nerve Discharge

Aortic depressor nerve discharge (AND), lumbar sympathetic nerve discharge (SND), and single-unit activity of medullospinal pressure-sensitive neurons of nucleus paragigantocellularis lateralis (PGCL neurons) were recorded in halothane-anesthetized 16-wk-old spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. The relationship between these variables and mean arterial pressure (MAP) was investigated. The gain of baroreceptor afferents was not significantly different between the strains, but corner MAP (intersection between linear ascending portion of curve and noise) was 38 mmHg higher in SHRs. The relationship between SND and MAP and that between PGCL neuronal activity and MAP were both characterized by a plateau (maximal activity) at low MAP followed by a linear reduction reaching zero at a level called cutoff MAP. The theoretical intersection between the plateau and the linear decremental portion of these curves was defined as a corner MAP. Values of corner MAP determined at the three levels (AND, SND, PGCL) were identical in a given strain and reset by a common value in SHRs (38-40 mmHg). The gain of baroreceptor reflex measured at all three sites as the slope of the linear incremental (AND) or decremental (PGCL and sympathetic chain) portion of the activity-MAP relationship was the same in WKY rats and in SHRs. Cutoff MAP measured in PGCL was identical to that measured in peripheral sympathetic system for a given strain. There was no significant difference in maximal discharge rate of PGCL neurons nor in lumbar SND and no interstrain difference in the proportion of SND that was suppressible by arterial baroreceptor feedback.(ABSTRACT TRUNCATED AT 250 WORDS)

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Enhanced sympathetic reactivity to glutamate stimulation in medulla oblongata of spontaneously hypertensive rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.268.4.h1499 ◽

1995 ◽

Vol 268 (4) ◽

pp. H1499-H1509 ◽

Cited By ~ 4

Author(s):

T. L. Yang ◽

C. Y. Chai ◽

C. T. Yen

Keyword(s):

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Significant Difference ◽

Baseline Adjustment ◽

Before And After ◽

Threshold Doses ◽

Wistar Kyoto ◽

Alpha Chloralose ◽

Renal Sympathetic

The distribution and reactivity of vasomotor sites in the ventrolateral (VLM) and dorsomedial medulla (DMM) of stroke-prone spontaneously hypertensive rats (SHRSP), spontaneously hypertensive rats (SHR), and Wistar-Kyoto rats (WKY) were compared. Rats were anesthetized with alpha-chloralose and urethan. Baroreceptor denervation and vagotomy were performed. L-Glutamate (Glu, 10 mM, 30 nl) was microinjected into the DMM or VLM to identify vasoactive sites. The extent and the patterns of distribution of these sites in the three strains of rats were similar. The dose-response curve of the vasoactive site was studied with 1–500 pmol of Glu. The maximum responses of blood pressure and renal sympathetic activity were larger and threshold doses of Glu were lower in hypertensive rats. The significance of the differences among the strains was analyzed before and after adjustment for baseline pressure or activity. Most of the differences were statistically significant before baseline adjustment. After baseline adjustment, many differences between the SHRSP and the WKY remained significant. However, the only significant difference detected between the SHR and the WKY was the threshold dose for eliciting renal sympathetic change in the caudal VLM. These results suggest that there may be a general increase in excitability of the vasomotor neurons in the medulla of the hypertensive rats.

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Successful vitrification of stroke-prone spontaneously hypertensive and normal Wistar rat 2-cell embryos

Laboratory Animals ◽

10.1258/002367796780865745 ◽

1996 ◽

Vol 30 (2) ◽

pp. 132-137 ◽

Cited By ~ 5

Author(s):

Masahiro Sato ◽

Kazuo Yokokawa ◽

Kazuhiro Kasai ◽

Norihiro Tada

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Room Temperature ◽

Wistar Rat ◽

Hypertensive Rats ◽

Phenotypic Characteristics ◽

Spontaneously Hypertensive ◽

Significant Difference ◽

One Step ◽

Wistar Kyoto

Stroke-prone spontaneously hypertensive rats (SHRSPs) have been widely used as models of hypertension and cerebral apoplexy. They were obtained by selective sib-breeding of Wistar Kyoto rats with higher blood pressure than rats of the original Wistar Kyoto strain. For vitrification of SHRSP 2-cell embryos, DPS solution containing 2.75 M dimethylsulfoxide, 2.75 M propylene glycol and 1.0 M sucrose was prepared and diluted in a modified phosphatebuffered saline, PBl, containing 0.3% bovine serum albumin. Embryos were exposed to the resulting solution in one step at room temperature, kept in the solution for 15 s, vitrified in liquid nitrogen, and warmed rapidly. The post-warming survival rate as morphologically assessed was 70% (148/210), which was comparable ( P>0.05) to the rate of 88% (78/89) for the solution control. After vitrification, the embryos were transferred into recipient animals, and 62% (48/78) were normally delivered, comparable ( P>0.05) to the percentage for the solution control (68%, 57/84). These was no significant difference between pups from vitrified embryos and those from unvitrified control embryos in either the growth curve or degree of blood pressure increase. These findings demonstrate the effectiveness of the simple vitrification method we used for cryopreservation of SHRSP and Wistar rat 2-cell embryos, and also demonstrate that vitrification-mediated cryopreservation does not affect the phenotypic characteristics of SHRSPs.

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