Wistar-Kyoto Groups Research Articles

Blood Pressure Lowering Effect of Cuban Policosanol is Accompanied by Improvement of Hepatic Inflammation, Lipoprotein Profile, and HDL Quality in Spontaneously Hypertensive Rats.

We investigated the antihypertensive effect of policosanol on spontaneously hypertensive rats (SHR). For this, we analyzed blood pressure, blood lipid, and lipoprotein properties in male SHR after consumption of Cuban policosanol (PCO). The experimental groups were as follows: normotensive Wistar Kyoto (WKY) control, SHR group fed normal diet (ND), SHR group fed 20 mg of PCO, SHR group fed 100 mg of PCO, and SHR group fed 200 mg of PCO per kg of body weight. After eight weeks, the SHR control group showed gradual increases up to 22% in systolic blood pressure (SBP) and 17.6% in the diastolic blood pressure (DBP) compared with values at week 0. However, policosanol consumption had a dose-dependent reduction effect on SBP and also reduced DBP up to 16% in a dose-dependent manner. Heart rate (HR) bpm increased by six percent in the SHR control, whereas the 20 mg, 100 mg, and 200 mg of policosanol groups showed a reduction of 36%, 28%, and 34% respectively. Although serum total cholesterol (TC) level of SHR was not affected by policosanol consumption (70–80 mg/dL), serum triglyceride (TG) level significantly decreased in the SHR + 200 mg of PCO group. Serum high-density lipoprotein cholesterol (HDL-C) level was also significantly elevated by policosanol consumption. The % HDL-C/TC ratio was elevated in the policosanol group up to 67–70%, whereas the SHR control group showed a ratio of 58%. Serum cholesteryl ester transfer protein (CETP) activity was reduced by policosanol in a dose-dependent manner. Although the serum glutamate oxaloacetate transaminase (GOT)/ glutamate pyruvate transaminase (GPT) were similar across all groups, policosanol consumption caused reduction of reactive oxygen species (ROS) levels in hepatic tissue. The SHR control group showed a 2.1-fold higher serum C-reactive protein (CRP) level than the WKY group, whereas the CRP level decreased in the SHR + 200 mg of PCO group (up to 45%) than SHR control group. Aldosterone level was reduced in the policosanol group (up to 34%) in a dose-dependent manner compared to the control. In conclusion, eight weeks of policosanol consumption in SHR resulted in remarkable reduction of blood pressure, serum aldosterone, and serum TG levels along with the elevation of HDL-C and improvement of hepatic inflammation.

Impairment of Protease-Activated Receptor 2-Induced Relaxation of Aortas of Aged Spontaneously Hypertensive Rat.

Hypertension is one of the most prevalent diseases worldwide and can cause harmful complications within the vascular system. Further research on vascular responsiveness to different ligands and diverse receptors in various arteries is required to understand the mechanisms underlying the development of these vascular complications. Here, we investigated the vasorelaxant effect of the protease-activated receptor 2 (PAR2) agonist 2-furoyl-LIGRLO-amide (2-Fly) and two commonest agents, namely endothelium-dependent dilator acetylcholine (ACh) and endothelium-independent dilator sodium nitroprusside (SNP), on the thoracic aorta isolated from aged spontaneously hypertensive rats (SHR) (age, 52±1 weeks). The effects of these agents were compared between aortas isolated from SHR and age-matched normotensive Wistar Kyoto (WKY) rats. Compared with the WKY group, in the SHR group, 2-Fly-induced relaxation was impaired, ACh-induced relaxation was slightly decreased at low concentrations, and SNP-induced relaxation was similar. In addition, 2-Fly-induced aortic relaxation was largely decreased by a PAR2 antagonist (FSLLRY), endothelial denudation, and a nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) but not by an Akt inhibitor. These results suggested that PAR2-induced relaxations of aortas of aged SHR was impaired, and this impaired aortic relaxation may be attributed to decreased NO bioavailability rather than altered NO sensitivity unrelated to the Akt activity.

The influence of benazepril and amlodipine on the expression of secretin and somatostatin in spontaneously hypertensive rats

Investigate the influence of benazepril and amlodipine on the expression of secretin (PZ) and somatostatin (SS) in spontaneously hypertensive rats (SHR). Forty-five SHRs (14 weeks old, male) were randomly assigned into 3 groups (n=15):SHR group, Benazepril group (which was given benazepril 0.90 mg·kg-1·d-1) and Amlodipine group (SHRs were given amlodipine 0.45 mg· kg-1·d-1), taking WistarKyoto(WKY) as normal control (n=15), meanwhile, rats in SHR group and WKY group were given the same volume of distilled water. After 8 weeks of intervention, the expression of protein and mRNA of PZ in duodenum and SS in sinuses ventriculi was detected by enzyme-linked immunoassay and RT-PCR. After 8 weeks of intervention, compared with the WKY group, the expression of protein and mRNA of PZ in duodenum and SS in sinuses ventriculi was increased significantly in SHR group (P<0. 05). Compared with SHR group, the expression of PZ in duodenum and SS in sinuses ventriculi was decreased significantly in Benazepril group and Amlodipine group (P<0.05). Compared with Benazepril group, in Amlodipine group the expression of PZ mRNA in duodenum and SS mRNA in sinuses ventriculi was decreased more significantly (P<0.05). The regulation disorder of PZ in duodenum and SS in sinuses ventriculi exists in SHR. The antihypertensive effect of benazepril and amlodipine may be realized by regulating the expression of PZ and SS, while the regulation of amlodipine is more obvious than benazepril.

Effect of Acupuncture at LR3 on Cerebral Glucose Metabolism in a Rat Model of Hypertension: A 18F-FDG-PET Study.

Our objective was to investigate the effect of acupuncture at LR3 on cerebral glucose metabolism in spontaneously hypertensive rats (SHRs). We used 18F-2-fluoro-deoxy-D-glucose positron emission tomography (18F-FDG-PET) to examine the effects of acupuncture at LR3 on cerebral glucose metabolism in SHRs. SHRs were randomly allocated to receive no treatment (SHR group), needling at LR3 (SHR + LR3 group), or sham needling (SHR + sham group). Rats received 10 min acupuncture once per day for 7 days and were compared to normotensive Wistar Kyoto (WKY) rats. Blood pressure (BP) measurement and PET were performed after the first needling and the 7-day treatment period. BP was lower in the SHR + LR3 group compared to the other SHR groups between 30 and 60 min after the first needling and at 24 and 48 h after the 7-day treatment period. Glucose metabolism in the motor, sensory, and visual cortices was decreased in SHR group compared to WKY group. Needling at LR3 was associated with decreased glucose metabolism in the dorsal thalamus, thalamus, and hypothalamus and with increased metabolism in the cerebellar anterior and posterior lobes, medulla oblongata, and sensory cortex compared to the SHR group. These findings suggest that LR3 acupuncture improves hypertension through a mechanism involving altered brain activation in SHRs.

Central administration of tert-butylhydroquinone attenuates hypertension via regulating Nrf2 signaling in the hypothalamic paraventricular nucleus of hypertensive rats

Reactive oxygen species (ROS) in the paraventricular nucleus (PVN) play a pivotal role in the pathogenesis of hypertension. Nuclear factor E2-related factor-2 (Nrf2) is an important transcription factor that modulates cell antioxidant defense response against oxidative stress. The present study aimed to explore the efficacy of PVN administration of tert-butylhydroquinone (tBHQ), a selective Nrf2 activator, in hypertensive rats. 16-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used in this study. These rats were chronic bilateral PVN infusion of tBHQ (0.8μg/day), or oxygen free radical scavenger tempol (20μg/h), or vehicle for 2weeks. SHR rats had higher mean arterial pressure (MAP), plasma norepinephrine (NE) levels, and sympathetic nerve activity (RSNA) and lower PVN levels of Nrf2, hemeoxygenase-1 (HO-1), superoxide dismutase-1 (SOD1) and catalase (CAT) as compared with those in the WKY group. Bilateral PVN infusion of tBHQ or tempol significantly reduced MAP, RSNA, plasma NE levels in SHR rats. In addition, tBHQ treatment enhanced the nuclear accumulation of Nrf2 and increased the expression of HO-1, CAT and SOD1 in SHR rats. Furthermore, tBHQ attenuated PVN levels of ROS, the expression of proinflammatory cytokines and restored the imbalance of neurotransmitters in PVN. Knockdown of Nrf2 in the PVN by adeno-associated virus mediated small interfering RNA abrogated the protective effects of tBHQ on hypertension. These findings suggest that PVN administration of tBHQ can attenuate hypertension by activation of the Nrf2-mediated signaling pathway.

Hypertension Editors' Picks: Hypertension and Sleep.

Hypertension Editors' Picks: Hypertension and Sleep.

Lentil consumption reduces resistance artery remodeling and restores arterial compliance in the spontaneously hypertensive rats

We previously established that lentils were able to significantly attenuate the development of hypertension in spontaneously hypertensive rats (SHRs), but the mechanism was not investigated. The current study was therefore designed to examine the effect of lentils on arterial function in relation to arterial stiffness, lipid biochemistry and activation of select aortic proteins. Seventeen-week-old male SHRs were randomly assigned to groups (n=10/group) fed (a) 30% w/w green lentils, (b) 30% red lentils, (c) 30% mixed lentils (red and green) or (d) no lentils for 8 weeks. Normotensive Wistar Kyoto (WKY) groups (n=10/group) received either the mixed lentil or no lentil diet. Blood pressure, pulse wave velocity and serum lipids were measured at baseline and 8 weeks, while pressure myography, arterial morphology and aortic proteins were measured after termination. There were no dietary-related changes in pulse wave velocity or blood pressure for any SHR or WKY group. Low-density lipoprotein cholesterol and high-density lipoprotein cholesterol were significantly lower in only SHR red lentil and WKY mixed lentil groups compared to their controls. The lentil diets reduced the media:lumen ratio of SHRs relative to control-fed SHRs but had no effect on WKYs. Both red and green lentils reduced arterial stiffness of SHRs but not WKYs. SHR lentil groups showed lower aortic p38 mitogen-activated protein kinase (p38MAPK) phosphorylation, thus implying that p38MAPK activation is suppressed with lentil feeding. Lentil-based diets suppress pathological vascular remodeling in SHRs, while green lentils maintain the vascular function of SHRs similar to normotensive WKYs despite the presence of high blood pressure.

Mechanisms Underlying Enhanced Noradrenaline-Induced Femoral Arterial Contractions of Spontaneously Hypertensive Rats: Involvement of Endothelium-Derived Factors and Cyclooxygenase-Derived Prostanoids.

We investigated the relationship between noradrenaline (NAd)-induced contractions, endothelial function, and hypertension in femoral arteries isolated from spontaneously hypertensive rats (SHR). In the femoral arteries of SHR, vs. age-matched control Wistar Kyoto (WKY) rats, contractions induced by NAd were increased. These effects were enhanced by endothelial denudation, which abolished the differences between the two groups. NAd-induced contractions were enhanced by nitric oxide (NO) synthase inhibition, and further increased by the blockade of endothelium-derived hyperpolarizing factor (EDHF). Conversely, NAd-induced contractions were inhibited by cyclooxygenase (COX) inhibition. In addition, in SHR arteries, acetylcholine-induced relaxation was reduced, and components of endothelium-derived factors were altered, such as increased COX-derived vasoconstrictor prostanoids, reduced EDHF, and preserved NO-mediated relaxation. In the femoral arteries of SHR, the production of prostanoids [6-keto prostaglandin (PG)F1α (a metabolite of prostacyclin (PGI2), PGE2, and PGF2α] and COX-2 protein were increased compared with that in WKY rats. By contrast, contractions induced by beraprost (a stable PGI2 analogue), PGE2, and U46619 (thromboxane/prostanoid receptor agonist) were similar between the SHR and WKY groups. Thus, NAd-induced femoral arterial contractions are augmented in SHR resulting from endothelial dysfunction and increased COX-derived vasoconstrictor prostanoid levels.

Comparative Analysis of Mechanical Properties of PWV, NO and Ascending Aorta between WHY Rats and SHR Rats.

The aim of this study was to compare and analyze the tensile mechanical properties of the ascending aorta (AA) in Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs), for the purpose of providing a biomechanical basis for hypertension prevention. Pulse wave velocities (PWV) and serum nitric oxide (NO) concentrations were determined in 6-month-old WKY rats and SHRs (n = 21, n = 21, respectively). Then, 20 AAs from each group were obtained for longitudinal tensile testing. The maximum stress, maximum strain, and strain at a tensile stress of 16 Kpa were greater in WKY rats than in SHRs (p < 0.05). The aortic elastic modulus and PWV value were greater in SHRs than in WKY rats (p < 0.05 for both), while NO concentrations were lower in the SHR group than in the WKY group (p < 0.05). The AA tensile mechanical properties differed between the WKY rats and SHRs, and the tensile mechanical properties of the SHR model had changed. Ascending aorta; Hypertension; Mechanical properties; Pulse wave velocity; SHR rats; WKY rats.

Pathological effects of obstructive apneas during the sleep cycle in an animal model of cerebral small vessel disease.

We tested the hypothesis that apneas during the sleep cycle exacerbate hypertension and accelerate changes that occur with cerebral small vessel disease. Obstructive sleep apnea was modeled by intermittent inflations of a chronically implanted tracheal balloon to occlude the airway during the sleep cycle (termed OSA) in spontaneously hypertensive stroke-prone (SHRSP) rats, a model of cerebral small vessel disease. SHRSP rats and their parent strain, Wistar Kyoto (WKY) rats, were exposed to OSA for 2 weeks (from 9 to 11 or from 18 to 20 weeks). At 9 weeks, hypertension was developing in the SHRSP rats and was firmly established by 18 weeks. OSA exposure increased systolic blood pressure in SHRSP rats by ≈30 mm Hg in both age groups compared with shams that were surgically prepared but not exposed to OSA (P<0.05). OSA exposure also increased systolic blood pressure in WKY rats by 20 and 37 mm Hg at 11 and 20 weeks, respectively (P<0.05). OSA exposure in SHRSP rats compromised blood-brain barrier integrity in white matter at both 11 and 20 weeks of age when compared with SHRSP sham rats (P<0.05). Microglia were activated in SHRSP rats exposed to OSA but not in sham rats at 11 weeks (P<0.05). At 20 weeks, microglia were activated in sham SHRSP rats (P<0.05) compared with WKY sham rats and were not further activated by OSA. Neither was blood-brain barrier integrity altered nor microglia activated in any of the WKY groups. We conclude that OSA accelerates the onset of the cerebral pathologies associated with cerebral small vessel disease in SHRSP, but not WKY, rats.

Effect of crowding stress on tolerance to ischemia-reperfusion injury in young male and female hypertensive rats: molecular mechanisms.

Sex and social stress may represent risk factors in the etiology of hypertension and heart response to ischemia-reperfusion (I/R) injury. Phosphatidylinositol 3-kinase/protein kinase B (Akt) plays an important role in the processes associated with hypertension and myocardial tolerance to I/R, and may be involved in myocardial stress reaction. The impact of chronic stress on the response to I/R was investigated in the hearts of 7-week-old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats of both sexes. Stress was induced by reducing living space to 70 cm(2)/100 g body mass of rat for 2 weeks, while the controls were kept at 200 cm(2)/100 g. Langendorff-perfused hearts, subjected to I/R, exhibited higher vulnerability to ventricular tachycardia in crowd-stressed SHR vs. the control rats, and this was more pronounced in the males. Myocardial infarction was not affected by crowding stress in any of the groups. Male and female SHR showed increased activation of cardiac Akt, whereas nitric oxide synthase activity (NOS) with pro-apoptotic signaling decreased in the males but was not altered in the females (vs. WKY rats). NOS was enhanced in the female SHR and WKY groups by comparison with the respective males. Stress only reduced NOS activity in the SHR groups, and without changes in apoptotic markers. In conclusion, we showed that stress in young SHR mainly affects the nonlethal markers for I/R, and has no impact on myocardial infarction and apoptosis, despite reduced NOS activity.

MP31-02 SELECTIVE α1A-ADRENOCEPTOR BLOCKER SILODOSIN AMELIORATES VENTRAL PROSTATIC ENLARGEMENT IN THE SPONTANEOUSLY HYPERTENSIVE RAT : POSSIBLE ROLE OF THE PROSTATIC BLOOD FLOW

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 2015MP31-02 SELECTIVE α1A-ADRENOCEPTOR BLOCKER SILODOSIN AMELIORATES VENTRAL PROSTATIC ENLARGEMENT IN THE SPONTANEOUSLY HYPERTENSIVE RAT : POSSIBLE ROLE OF THE PROSTATIC BLOOD FLOW Shogo Shimizu, Panagiota Tsounapi, Takahiro Shimizu, Youichirou Higashi, Kumiko Nakamura, Felix Holmstrom, Masashi Honda, Keiji Inoue, and Motoaki Saito Shogo ShimizuShogo Shimizu More articles by this author , Panagiota TsounapiPanagiota Tsounapi More articles by this author , Takahiro ShimizuTakahiro Shimizu More articles by this author , Youichirou HigashiYouichirou Higashi More articles by this author , Kumiko NakamuraKumiko Nakamura More articles by this author , Felix HolmstromFelix Holmstrom More articles by this author , Masashi HondaMasashi Honda More articles by this author , Keiji InoueKeiji Inoue More articles by this author , and Motoaki SaitoMotoaki Saito More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1357AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A selective α1A-adrenoceptor blocker silodosin is known to increase the bladder blood flow in the spontaneously hypertensive rat (SHR), and consequently improve lower urinary tract symptoms. A decreased prostatic blood flow (PBF) could be one of the risk factors for benign prostatic enlargement (BPE). In the present study, the effect of silodosin was investigated in the SHR prostate as a BPE model. METHODS Twelve-week-old male SHRs were administered silodosin per orally (100, 300 μg/kg/day) once daily for 6 weeks. Wistar-kyoto (WKY) rats were used as normotensive controls. The control SHR and WKY rat groups were treated with vehicle. The effects of silodosin on blood pressure and PBF were estimated. Then, the tissue levels of oxidative stress marker (MDA), inflammatory cytokines (IL-6, CXCL1/CINC1 and TNF-α), and prostatic growth factors (TGF-β1, bFGF and α-SMA) were measured. The histological evaluation was performed by H&E staining. RESULTS There was a significant increase in blood pressure, MDA, IL-6, CXCL1/CINC1, TNF-α, TGF-β1, bFGF and α-SMA in the SHRs compared to WKY rats. On the other hand, the PBF was decreased in the SHRs. Moreover, the ventral prostate in the SHR group showed epithelial cells being taller in the shape. Both doses of silodosin significantly reversed the above parameters of SHRs to almost identical levels to the ones of the WKY group excluding the blood pressure. CONCLUSIONS A decreased PBF could induce the proliferative factors via release of oxidative stress and inflammatory cytokines in the SHR prostate. Silodosin may improve the BPE by increasing the PBF. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e355-e356 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shogo Shimizu More articles by this author Panagiota Tsounapi More articles by this author Takahiro Shimizu More articles by this author Youichirou Higashi More articles by this author Kumiko Nakamura More articles by this author Felix Holmstrom More articles by this author Masashi Honda More articles by this author Keiji Inoue More articles by this author Motoaki Saito More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Effects of rosuvastatin correlated with the down-regulation of CYP4A1 in spontaneously hypertensive rats

The effects of long-term rosuvastatin treatment on the regulation of cytochrome P450 (CYP) 4A1 expression and vascular homeostasis of spontaneously hypertensive rat (SHR) are still unknown. In this study SHRs were randomly divided into three groups (n=10 per group): SHR group, H-Rv group (rosuvastatin 2.5mg·kg−1·d−1), L-Rv group (rosuvastatin 0.5mg·kg−1·d−1), and 10 male Wistar–Kyoto (WKY) rats in the control group (WKY group). All rats were treated with rosuvastatin for 12weeks. The systolic blood pressure (SBP), left ventricle weight index (LVWI) and plasma lipids were measured during or after treatment. The expression of CYP4A1 mRNA and protein in different tissues was detected by real-time PCR and Western blot. In the heart, kidney and aorta, the CYP4A1 expressions were down-regulated at both mRNA and protein levels in rosuvastatin-treated groups compared with the untreated SHR group (P<0.05 or P<0.01), and high-dose rosuvastatin exerted a stronger down-regulatory effect. The increasing trend of blood pressure was markedly blunted in the rosuvastatin-treated groups versus the untreated SHR group, and a stronger effect was observed in high-dose group (P<0.05 and P<0.01 at different time points). LVWI, an indicator of ventricle hypertrophy, was improved in the high-dose group compared with the untreated SHR group (P<0.05). The plasma concentrations of TC, TG and LDL-C in three SHR groups (high-dose, low-dose and untreated group) were all significantly lower than those of WKY group (P<0.05 or P<0.01), which seemed unrelated to the treatment of rosuvastatin. These findings suggested that hypertension in SHRs was possibly associated with CYP4A1 overexpression, and the effects of rosuvastatin on blood pressure and ventricle hypertrophy were potentially correlated with CYP4A1 and its metabolite other than lipid profiles. Multiple mechanisms are likely involved in the beneficial effects of statins with respect to the regulation of CYP4A1.

Glomerular Damage in Experimental Proliferative Glomerulonephritis Under Glomerular Capillary Hypertension

Background/Aims: Immunologically and hemodynamically mediated the destruction of glomerular architecture is thought to be the major causes of end-stage renal failure. The purpose of this study is to evaluate the effect of glomerular hypertension on glomerular injury and the progression of glomerular sclerosis after Thy-1 nephritis was induced. Method: Thy-1 nephritis was induced in the stroke-prone spontaneously hypertensive rat strain (SHR-SP) (group SP) and in age-matched Wistar-Kyoto (WKY) (group WKY) rats, following unilateral nephrectomy (UNX), and a vehicle was injected alone in UNX SHR-SP as control (group SC). Result: The degree of glomerular damage in response to a single dose of anti-thy-1 antibody, and its functional consequences (eg. proteinuria, diminished GFR) are more pronounced in group SP than normotensive group WKY and hypertensive group SC without mesangial cell injury. While normotensive group WKY rats recovered completely from mesangial cell injury on day 28-42, glomeruli in group SP kept on persistent macrophage infiltration, α-SMA expression on day 42-56. In addition, glomerular capillary repair with the GECs was rarely seen in pronouncedly proliferative and sclerostic areas. The incidence of glomerular sclerosis and the level of proteinuria were markedly increased by day 56 in the group SP. Conclusions: Our results demonstrate that glomerular hypertension aggravate glomerular damage and glomerulosclerosis in this model of Thy 1 nephritis.

Antiaging gene Klotho regulates endothelin-1 levels and endothelin receptor subtype B expression in kidneys of spontaneously hypertensive rats.

Klotho is an antiaging gene and is predominately expressed in kidneys. The endothelin system is critical in the regulation of kidney function. The objective of this study is to assess whether klotho affects the renal endothelin system in spontaneously hypertensive rats (SHRs). Four groups of male SHRs and one group of male Wistar-Kyoto (WKY) rats were used. In-vivo expression of klotho was achieved by AAV2 delivery of mouse klotho full-length cDNA (AAV.mKL). Four groups of SHRs were given (intravenously) AAV.mKL, AAV.LacZ, AAV.GFP, and phosphate-buffered saline, respectively. The WKY group was given phosphate-buffered saline and served as a control. At the end of week 12 after gene delivery, all animals were euthanized. Plasma endothelin-1 (ET-1) and renal ET-1 levels were increased in SHRs vs. WKY rats. In-vivo expression of klotho reversed the elevated ET-1 levels in SHRs. ETB receptor protein expression was decreased in both kidney cortex and medulla of SHRs. Interestingly, in-vivo expression of klotho abolished the downregulation of ETB protein expression in SHRs, suggesting that klotho regulates ETB receptor expression. Klotho gene delivery also eliminated the increase in the ratio of ETA/ETB in SHRs. Mitochondrial superoxide dismutase (Mn-SOD) protein expression was decreased in kidneys of SHRs, which was rescued by in-vivo expression of klotho. Klotho gene delivery abolished the upregulation of ET-1 levels and the downregulation of ETB and Mn-SOD expression in kidneys of SHRs. These findings revealed a previously unidentified role of klotho in the regulation of the renal ET system and Mn-SOD in SHRs.

Long-term treatment of spontaneously hypertensive rats with losartan and molecular basis of modulating Ito of ventricular myocytes

The present study aimed to determine the effect of chronic treatment with losartan on transient outward potassium current (Ito) and the expression levels of potassium voltage-gated channel subfamily D members 2 and 3 (Kv4.2 and 3) and voltage-gated potassium channel-interacting protein 2 (KChIP2) in rats. Spontaneously hypertensive (SH) rats and Wistar-Kyoto (WKY) rats were used in the study. The rats were divided into lo-SH and SH groups and los-WKY and WKY groups, respectively. Ito was recorded and expression levels of Kv4.2, Kv4.3 and KChIP2 were measured by western blot analysis and quantitative polymerase chain reaction. Ito current density was smaller in SH compared with WKY, los-WKY and los-SH groups (P<0.01). Inactivation time constant of myocytes was larger in SH compared with WKY, los-WKY and los-SH groups (P<0.01). The mean levels of mRNA and protein of Kv4.2 and Kv4.3 were significantly lower in the SH compared with WKY, los-WKY and los‑SH groups in vivo and in vitro (P<0.01). The Pearson statistical test showed no correlation between the expression levels of Kv4.2, Kv4.3, KChIP2 and the changes in blood pressure in the losartan treatment group. In conclusion, chronic blockade of angiotensin II type 1 receptors with losartan reversed SH rats' electrical remodeling and shortened action potential duration, which was associated with an increase in Ito density as the expression levels of Kv4.2, Kv4.3 increased and the expression levels of KChIP2 decreased. However, the expression levels of Kv4.2, Kv4.3 and KChIP2 were not correlated with the change in blood pressure in the losartan treatment group. Losartan may decrease the inactivation time by increasing the expression of KChIP2.

Characterizing dynamic properties of retinal vessels in the rat eye using high speed imaging

PurposeThe dynamic properties of retinal vessels including pulse wave propagation and pulsatility index provide new perspective in retinal hemodynamic analysis. In this study we utilize a high speed imaging system to capture these characteristics in the rat eye for the first time. MethodsRetinal video images of 9 Wistar-Kyoto (WKY) rats were captured at a rate of 250 frames per second for 10s with a 50° field of view using a high speed camera (Optronis, Kehl, Germany). Two recordings were taken from each rat at the same sites for repeatability analysis. The electrocardiogram (ECG) was measured simultaneously with retinal images. Arterial retinal pulse wave velocity (rPWV) and arterial/venous pulse amplitude were calculated from recorded images. Arterial measurements were repeated in another normotensive strain of the same age (Sprague–Dawley, n=4). ResultsThe average WKY rPWV was 11.4±6.1cm/s. The differences between repeated measures were not significant (−2.8±2.9cm/s, p=0.2). Sprague–Dawley animals had a similar rPWV (9.8±2.2cm/s, p=0.61). The average arterial and venous pulse amplitude was 7.1±1.5μm and 8.2±2.0μm respectively. There was a positive correlation between rPWV and heart rate in the WKY groups (r2=0.32). A positive correlation was also obtained between arterial and venous diameter and their pulse amplitude (r2=0.67 and r2=0.37 respectively). ConclusionrPWV was associated with heart rate. Higher pulsation amplitude was also correlated with larger vessel diameter. High speed imaging of retinal vessels in the rat eye provides an accurate and robust method to study dynamic characteristics of these vessels and their relationship with ocular and systemic abnormalities.

Moderate intensity exercise does not modulate myostatin and follistatin gene expression in the gastrocnemius muscle of spontaneously hypertensive rats with heart failure

The myostatin/follistatin pathway modulates skeletal muscle trophism. Physical exercise has an important role in the heart failure treatment. In this study we evaluated the effects of moderate aerobic physical training on myostatin and follistatin gene expression and trophism in the gastrocnemius of spontaneously hypertensive rats with heart failure. Sixteen‐month‐old SHRs and normotensive Wistar‐Kyoto (WKY) rats were assigned to sedentary or trained groups. Exercise was performed on treadmill, 30 min/day, 5 days/week, 12 m/min for 4 months. Transthoracic echocardiogram was performed at the end of experiment. Gene expression was evaluated by real time RT‐PCR. Fiber cross‐sectional area was measured in HE‐stained histological sections.Statistical analysistwo‐way ANOVA and Tukey.ResultsEchocardiography showed left cardiac chambers dilation and left ventricular systolic and diastolic dysfunction in both SHR groups compared to the WKY groups. Gene expression of myostatin and follistatin did not differ between groups. Cross‐sectional area was reduced in both SHR groups compared to WKY and was not changed by exercise.ConclusionPhysical exercise does not modulate skeletal muscle trophism and myostatin and follistatin gene expression in spontaneously hypertensive rats with heart failure.

Exercise Training Lowers the Enhanced Tonically Active Glutamatergic Input to the Rostral Ventrolateral Medulla in Hypertensive Rats

It is well known that low-intensity exercise training (ExT) is beneficial to cardiovascular dysfunction in hypertension. The tonically active glutamatergic input to the rostral ventrolateral medulla (RVLM), a key region for control of blood pressure and sympathetic tone, has been demonstrated to be increased in hypertensive rats. The aim of this study was to determine the effect of ExT on the increased glutamatergic input to the RVLM in spontaneously hypertensive rat (SHR). Normotensive rats Wistar-Kyoto (WKY) and SHR were treadmill trained or remained sedentary (Sed) for 12 weeks and classed into four groups (WKY-Sed, WKY-ExT, SHR-Sed, and SHR-ExT). The release of glutamate in the RVLM and its contribution to cardiovascular activity were determined in WKY and SHR after treatment of ExT. Blood pressure and sympathetic tone were significantly reduced in SHR after treatment with ExT. Bilateral microinjection of the glutamate receptor antagonist kynurenic acid (2.7 nmol in 100 nL) into the RVLM significantly decreased resting blood pressure, heart rate, and renal sympathetic nerve activity in SHR-Sed but not in WKY groups (WKY-Sed and WKY-ExT). However, the degree of reduction in these cardiovascular parameters evoked by KYN was significantly blunted in SHR-ExT compared with SHR-Sed group. The concentration of glutamate and the protein expression of vesicular glutamate transporter 2 in the RVLM were significantly increased in SHR-Sed compared with WKY-Sed, whereas they were reduced after treatment with ExT. Our findings suggest that ExT attenuates the enhancement in the tonically acting glutamatergic input to the RVLM of hypertensive rats, thereby reducing the sympathetic hyperactivity and blood pressure.

An animal study to compare the degree of the suppressive effects on the afferent pathways of micturition between tamsulosin and sildenafil

BackgroundTamsulosin, an α1-adrenoceptor antagonist, and sildenafil, a phosphodiesterase (PDE) inhibitor, are reported to improve lower urinary tract symptoms including overactive bladder (OAB). This study is aimed at investing the effects of tamsulosin and sildenafil and comparing the degree of the suppressive effects on the afferent pathways of micturition between them using an animal model of OAB, the spontaneously hypertensive rat (SHR).ResultsThe cystometric parameters, the basal pressure and duration of bladder contraction, were significantly increased in the SHR group as compared with the Wistar-Kyoto (WKY) group. The intercontraction interval also significantly decreased in the SHR group. In the SHR-Tam 0.01 mg/kg group and the SHR-Sil 1 mg/kg group, however, the basal pressure and duration were significantly reduced and the intercontraction interval was significantly prolonged. Moreover, the degree of the expression of c-Fos and NGF was significantly higher in the SHR group as compared with the WKY group. But it was significantly reduced in the SHR-Tam 0.01 mg/kg group and the SHR-Sil 1 mg/kg group. Furthermore, tamsulosin had a higher degree of effect as compared with sildenafil.ConclusionsIn conclusion, α1-adrenergic receptor antagonists and PDE-5 inhibitors may have an effect in improving the voiding functions through an inhibition of the neuronal activity in the afferent pathways of micturition.