Changes in the Urinary Metabolites in Losartan-Treated Spontaneously Hypertensive Rats

Introduction: This study examined the association of losartan induced changes in urinary metabolomic profile with the changes in blood pressure (BP) and renin-angiotensin- aldosterone system (RAAS) in spontaneously hypertensive rats (SHR). Methods: Male SHR were administered with either 0.5 mL of distilled water (control group, n=6) or 10 mg.kg -1 of losartan (group 2, n=6) daily by oral gavage for 4 weeks. Body weight, BP, food and water intake were measured weekly. At week 4, urine was collected for urinary electrolyte analysis and metabolite profiling, after which the animals were euthanised by decapitation and blood was collected for analysis of components of RAAS and electrolyte concentrations. Urine metabolite profile of SHR was determined using proton nuclear magnetic resonance ( 1 H-NMR) spectrometry combined with multivariate data analysis. Results: At week 4, losartan- treated SHR had significantly lower BP than non-treated SHR. There were no differences in water and food intake, body weight, serum and urinary electrolyte concentrations or in their urinary excretions between the two groups. No differences were evident in the components of RAAS except that the angiotensinogen level was significantly higher in losartan-treated SHR compared to non-treated SHR. Orthogonal partial least squares discriminant analysis (OPLS-DA) showed clear separation of urinary metabolites between control and losartan-treated SHR. Losartan-treated SHR group was separated from the control group by changes in the intermediates involved in glycine, serine and threonine metabolism. Conclusion: Antihypertensive effect of losartan in SHR seems to be associated with changes in urinary metabolite profile, particularly involving the metabolism of glycine, serine and threonine.

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Effect of chlorothiazide on serial measurements of exchangeable sodium and blood pressure in spontaneously hypertensive rats

Clinical Science ◽

10.1042/cs0690511 ◽

1985 ◽

Vol 69 (5) ◽

pp. 511-515 ◽

Cited By ~ 2

Author(s):

P. J. O. Manhem ◽

S. A. Clark ◽

W. B. Brown ◽

G. D. Murray ◽

J. I. S. Robertson

Keyword(s):

Blood Pressure ◽

Body Weight ◽

Spontaneously Hypertensive Rats ◽

Tap Water ◽

Treated Group ◽

Temporal Association ◽

Control Group ◽

Exchangeable Sodium ◽

Hypertensive Rats ◽

Spontaneously Hypertensive

1. Chlorothiazide (100 mg/kg body weight) was given by gavage daily to spontaneously hypertensive rats for 4 weeks. Another group of spontaneously hypertensive rats was given only tap water and served as control. 2. Measurements of total exchangeable sodium, blood pressure and weight were performed for 2 weeks before and for 4 weeks during treatment. 3. Before treatment, exchangeable sodium, blood pressure and weight were similar in the two groups of rats. 4. Chlorothiazide significantly attenuated the blood pressure increase in spontaneously hypertensive rats, the effect being most marked during the first 2 1/2 weeks of treatment and less thereafter. 5. Rats in the chlorothiazide-treated group gained weight more slowly than did those of the control group. 6. Exchangeable sodium, expressed as mmol/kg body weight, did not differ significantly between the two groups at any stage. 7. When exchangeable sodium was expressed as mmol/rat, there was a more gradual rise in the chlorothiazide-treated animals, in accordance with their slower gain in weight. 8. There was no temporal association between the antihypertensive effect of chlorothiazide and changes in exchangeable sodium. 9. Thus whereas chlorothiazide treatment of spontaneously hypertensive rats slows the increase of both weight and exchangeable sodium, other mechanisms are apparently responsible for the antihypertensive action of the drug.

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Fully hydrogenated canola oil extends lifespan in stroke-prone spontaneously hypertensive rats

Lipids in Health and Disease ◽

10.1186/s12944-021-01540-7 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Kenjiro Tatematsu ◽

Daisuke Miyazawa ◽

Yoshiaki Saito ◽

Harumi Okuyama ◽

Naoki Ohara

Keyword(s):

Body Weight ◽

Canola Oil ◽

Spontaneously Hypertensive Rats ◽

Body Weight Gain ◽

Basal Diet ◽

The Body ◽

Control Group ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Hydrogenated Oils

Abstract Background Canola oil (Can) and several vegetable oils shorten the lifespan of stroke-prone spontaneously hypertensive rats (SHRSP). Although similar lifespan shortening has been reported for partially hydrogenated Can, the efficacy of fully hydrogenated oils on the lifespan remains unknown. The present study aimed to investigate the lifespan of SHRSP fed diets containing 10 % (w/w) of fully hydrogenated Can (FHCO) or other oils. Methods Survival test: Upon weaning, male SHRSP were fed a basal diet for rodents mixed with one of the test oils —i.e., FHCO, Can, lard (Lrd), and palm oil (Plm) throughout the experiment. The animals could freely access the diet and drinking water (water containing 1 % NaCl), and their body weight, food intake, and lifespan were recorded. Biochemical analysis test: Male SHRSP were fed a test diet with either FHCO, Can, or soybean oil (Soy) under the same condition, except to emphasize effects of fat, that no NaCl loading was applied. Soy was used as a fat source in the basal diet and was set the control group. Blood pressures was checked every 2 weeks, and serum fat levels and histological analyses of the brain and kidney were examined after 7 or 12 weeks of feeding. Results During the survival study period, the food consumption of FHCO-fed rats significantly increased (15–20 % w/w) compared with that of rats fed any other oil. However, the body weight gain in the FHCO group was significantly less (10–12 %) than that in the control group at 9–11 weeks old. The FHCO (> 180 days) intervention had the greatest effect on lifespan, followed by the Lrd (115 ± 6 days), Plm (101 ± 2 days), and Can (94 ± 3 days) diets. FHCO remarkably decreased the serum cholesterol level compared with Can and the systolic blood pressure from 12 to 16 weeks of age. In addition, while some rats in the Can group exhibited brain hemorrhaging and renal dysfunction at 16 weeks old, no symptoms were observed in the FHCO group. Conclusion This current study suggests that complete hydrogenation decreases the toxicity of Can and even prolongs the lifespan in SHRSP.

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Effects of Chronic Eta-Receptor Blockade in Stroke-Prone Spontaneously Hypertensive Rats.

Hypertension ◽

10.1161/hyp.36.suppl_1.699-e ◽

2000 ◽

Vol 36 (suppl_1) ◽

pp. 699-700

Author(s):

Christine Elise Barandier ◽

Zhihong Yang ◽

Thomas Felix Luscher

Keyword(s):

Blood Pressure ◽

Body Weight ◽

Spontaneously Hypertensive Rats ◽

Treated Group ◽

The Body ◽

Cerebral Injury ◽

Control Group ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Eta Receptor

P38 It has been reported that some ET-receptor blockers prevent cerebral injury in stroke-prone spontaneously hypertensive rats (SPSHR), whereas chronic inhibition of nitric oxide synthase (NOS) precipitates stroke. We investigated the protective effects of chronic treatment with BSF208075, a selective ETA-receptor blocker in SPSHR treated with the NOS inhibitor, L-NAME, or untreated. 4 groups of male SPSHR, 10 week old, were studied: a control group and 3 groups treated with BSF208075 (30 mg/kg/day), L-NAME (10 mg/kg/day) or BSF208075+L-NAME (30 and 10 mg/kg/day, respectively). Systolic blood pressure, body weight and survival were recorded. In the control group, severe hypertension (292.3±1.0mmHg; p<0.01 vs baseline) developed within 4 weeks. In contrast, in the BSF208075-treated group, the development of hypertension (265.2±3.8mmHg; p<0.01 vs control) was limited and blood pressure started to decrease after 4 weeks of treatment. In both of these groups, the increase in body weight was normal and similar, and 90% of the animals were still alive after 50 days of treatment. In the L-NAME-treated group, the blood pressure immediately and drastically increased, the body weight was reduced by 50% within 6 weeks of treatment. 50% of mortality was observed after 22 days of treatment, and all rats died within 36 days. The mean survival was 25.9±2.4 days. In L-NAME+BSF208075-treated group, BSF208075, although it did not prevent the development of hypertension, it reduced the loss of body weight and increased mean survival to 36.7±1.4 days (p<0.01 vs L-NAME-treated group). In this group, 50% of mortality was observed after 37 days of treatment, and all rats died within 41 days. These results show that BSF208075 delays the development of hypertension in SPSHR, and increases survival of L-NAME-treated SPSHR, independent of hypertension.

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Abstract 309: Role of Hemeoxygenase in the Reno-Protective Effects of Soluble Epoxide Hydrolase Inhibition In Diabetic Spontaneously Hypertensive Rats

Hypertension ◽

10.1161/hyp.60.suppl_1.a309 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Ahmed A Elmarakby ◽

Jessica Faulkner ◽

Chelsey Pye ◽

Babak Baban ◽

Katelyn Rouch ◽

...

Keyword(s):

Protective Effect ◽

Renal Injury ◽

Renal Fibrosis ◽

Spontaneously Hypertensive Rats ◽

Epoxide Hydrolase ◽

Soluble Epoxide Hydrolase ◽

Control Group ◽

Protective Effects ◽

Hypertensive Rats ◽

Spontaneously Hypertensive

We previously showed that inhibition of soluble epoxide hydrolase (sEH) increased epoxyeicosatrienoic acids (EETs) levels and reduced renal injury in diabetic mice and these changes were associated with induction of hemeoxygenase-1 (HO-1). The present study determines whether the inhibition of HO negates the reno-protective effect of sEH inhibition in diabetic spontaneously hypertensive rats as a model of diabetic nephropathy in which hypertension coexists with diabetes. After six weeks of induction of diabetes with streptozotocin, SHR were divided into the following groups: untreated, treated with the sEH inhibitor, trans -4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (AUCB), treated with the HO inhibitor, stannous mesoporphyrin (SnMP), and treated with both inhibitors for four more weeks; non diabetic SHR served as a control group. Although inhibition of sEH increased renal EETs/DHETEs ratio and HO-1 activity in diabetic SHR, it did not significantly alter blood pressure (plasma EETs/DHETEs ratio was 0.5± 0.1 in AUCB-treated vs. 0.1± 0.01 in untreated diabetic SHR, P<0.05). Treatment of diabetic SHR with AUCB reduced the elevation in urinary albumin and nephrin excretion (albuminuria was 6.5± 0.5 in AUCB-treated diabetic SHR vs. 9± 1.7 mg/day in untreated diabetic SHR and nephrinuria was 70±11 in AUCB-treated diabetic SHR vs. 111± 9 μg/day in untreated diabetic SHR, P<0.05) whereas co-administration of SnMP with AUCB prevented these changes (albuminuria was 10.6± 0.6 mg/day and nephrinuria was 91±11 μg/day). Immunohistochemical analysis revealed elevations in renal fibrosis and apoptosis as evidenced by increased renal TGF-β, fibronectin and annexin V expression in diabetic SHR and these changes were reduced with sEH inhibition. Co-administration of SnMP with AUCB prevented its ability to reduce renal fibrosis and apoptosis in diabetic SHR. In addition, SnMP treatment also prevented AUCB-induced decreases in renal macrophage infiltration and renal TGF-β, NFκB and MCP-1 levels in diabetic SHR. These data suggest that HO-1 induction is involved in the protective effect of sEH inhibition against diabetic renal injury.

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System-based DNA microarray analyses of different gene expression profile in spontaneously hypertensive rats treated with Songling Xuemaikang Capsule reveals underlying causal mechanisms.

10.21203/rs.2.14612/v1 ◽

2019 ◽

Author(s):

Li-tao Liu ◽

Cui-qi Yan ◽

Qiao-xin Tang ◽

Man-xi Zhao ◽

Chuan-zhen Teng ◽

...

Keyword(s):

Gene Expression ◽

Vascular Remodeling ◽

Spontaneously Hypertensive Rats ◽

Control Group ◽

Causal Network ◽

Ang Ii ◽

Dosage Group ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Songling Xuemaikang Capsule

Abstract Background: Hypertension is considered the major risk factor for human health in the world. Songling Xuemaikang Capsule (SXC) is clinically used as a medicine for the prevention and treatment of cardiovascular and cerebrovascular diseases such as hypertension and hyperlipidemia. However, the underlying mechanisms have yet to be fully identified. Methods: Valsartan, as a positive control drug, high- and low-dose of SXC were orally administration with for 28 days to investigate the anti-hypertensive effect of SXC in spontaneously hypertensive rats (SHRs). The serum levels of aldosterone and Angiotensin II (Ang II) were detected. The gene expression profiling was performed in the thoracic aorta of SHRs using the Whole Rat Genome Oligo nucleotide Microarray. The integrated causal network analysis was performed to understand the mechanism of antihypertensive effect of SXC. Results: The results shown that the systolic and diastolic blood pressure were significant decreased in SXC low-dosage group and high-dosage group compared with the control group respectively. SXC low and high-dosage treatment decreased serum aldosterone levels significantly but increased serum Ang II compared with the control group respectively. Causal network analysis shown that treatment with SXC reversing the vascular remodeling process, inhibiting vascular inflammation and atherosclerosis, reversing endothelial cells dysfunction and likely reducing peripheral vascular resistance by down-regulated processes related to vascular remodeling, dyslipidemia, the complement system, leukocyte rolling, and endothelial dysfunction. In addition, SXC treatment may also activate fibrinolysis and regulate lipid and glucose metabolism. Conclusions: Those obtained data could help our understanding and potential utilization of SXC in the treatment or prevention of hypertension。

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Beneficial effect of simvastatin and pravastatin treatment on adverse cardiac remodelling and glomeruli loss in spontaneously hypertensive rats

Clinical Science ◽

10.1042/cs20040292 ◽

2005 ◽

Vol 108 (4) ◽

pp. 349-355 ◽

Cited By ~ 39

Author(s):

Daniele G. BEZERRA ◽

Carlos A. MANDARIM-de-LACERDA

Keyword(s):

Left Ventricle ◽

Spontaneously Hypertensive Rats ◽

Renal Cortex ◽

Interstitial Fibrosis ◽

Treated Group ◽

Left Ventricular ◽

Control Group ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Significant Difference

The aim of the present study was to investigate the possibility of different effects of the hydrophobic statin simvastatin and the hydrophilic statin pravastatin on the remodelling process in the overloaded left ventricle and renal cortex of SHRs (spontaneously hypertensive rats). Fifteen SHRs were treated for 40 days with simvastatin, pravastatin or placebo (water) via orogastric administration. Left ventricle and renal cortex were examined by light microscopy and stereology. LV (left ventricular) cardiomyocyte nuclei (N[cmn]) and glomeruli (N[gl]) numbers were estimated by the dissector method. BP (blood pressure) and serum triacylglycerols (triglycerides) were lower in the statin-treated groups than in the untreated control group. The volume density of the interstitial connective tissue was smaller and length density of the intramyocardial arteries, as well as the arteries/cardiomyocyte ratio, was greater in the statin-treated groups than in the control group. No difference was observed between the two statin-treated groups. The cross-sectional cardiomyocyte area was significantly smaller in the simvastatin-treated group than in the control or pravastatin-treated groups, and it was smaller in the pravastatin-treated group than in the control group. N[cmn] and N[gl] were greater in the two statin-treated groups than in the control group, but no significant difference was observed between the two statin-treated groups. In conclusion, administration of the statins simvastatin and pravastatin to SHRs effectively prevented the elevation in BP and serum triaclyglycerols, and also attenuated adverse cardiac and kidney remodelling by preventing LV hypertrophy, enhancing myocardial vascularization with the decrease in interstitial fibrosis and attenuating cardiomyocyte and glomerular loss.

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Effect of Curcuma Herbs on Vasomotion and Hemorheology in Spontaneously Hypertensive Rat

The American Journal of Chinese Medicine ◽

10.1142/s0192415x05003053 ◽

2005 ◽

Vol 33 (03) ◽

pp. 449-457 ◽

Cited By ~ 17

Author(s):

Hirozo Goto ◽

Yohei Sasaki ◽

Hirotoshi Fushimi ◽

Naotoshi Shibahara ◽

Yutaka Shimada ◽

...

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Spontaneously Hypertensive Rat ◽

Radical Scavenging ◽

Male Rats ◽

Control Group ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Scavenging Effect ◽

Low Shear Stress

Curcuma herbs have a vasodilator effect. The effects of C. longa, which induces only endothelium-independent vasodilatation, and C. zedoaria, which induces both endothelium-dependent and -independent vasodilatation, were studied on vasomotion and hemorheology in spontaneously hypertensive rats. Spontaneously hypertensive eight-week-old male rats were assigned to five groups. For 12 weeks, the control group received standard chow. The 3%CL (C. longa) group received standard chow containing 3% (wt/wt) C. longa. The 1%CZ and 3%CZ (C. zedoaria) groups received standard chow containing 1% and 3% (wt/wt) C. zedoaria, respectively. The captoril group received standard chow and 100 mg/kg/day of captoril in drinking water. Blood pressure, vasomotion, hemorheology, etc. were examined. Systolic blood pressure of the 3%CZ and captoril groups decreased significantly as compared to the control group. Acetylcholine-induced endothelium-dependent relaxations of the 3%CZ and captoril groups were increased to a greater degree, significantly, than the control group. When testing xanthine oxidase-induced contraction, the 3%CZ group was significantly decreased as compared to the control group. Low shear stress of whole blood viscosity showed the 3%CL and 3%CZ groups to be decreased significantly compared to the control group. Thus, Curcuma herbs have hypotensive and protective effect on the endothelium in spontaneously hypertensive rats. Especially, C. zedoaria is more effective than C.longa, and its mechanism is thought to be related to a radical scavenging effect and improvement of hemorheology.

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Effect of Yishenjiangyafang on Plasma Metabolomics in Senile Spontaneously Hypertensive Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8868267 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Lei Zhang ◽

Jie Yu ◽

Yingying Liu ◽

Weixing Guo ◽

Yunlun Li

Keyword(s):

Blood Pressure ◽

Treatment Group ◽

Group Treatment ◽

Metabolic Pathways ◽

Spontaneously Hypertensive Rats ◽

Control Group ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Q Exactive ◽

Wistar Kyoto

Objectives. Yishenjiangyafang is a traditional Chinese medicine used to clinically treat hypertension. This study aimed to explore the effect of yishenjiangyafang on plasma metabolomics in senile spontaneously hypertensive rats (SHRs). Methods. Twelve 50-week-old SHR (6 males and 6 females) were randomly divided into two groups: a treatment group, in which rats were intragastrically administered with yishenjiangyafang (10.08 g kg−1·d−1), and a model group, in which all SHRs were administered the same volume of saline. Six age- and gender-matched Wistar–Kyoto (WKY) rats were used as the control group. Treatment was given for 6 days per week and lasted for 8 weeks. Systolic and diastolic blood pressures of the rats were measured with the noninvasive tail artery pressure measurement system. An ultraperformance liquid chromatography quadruple electrostatic field orbit (UPLC-Q-Exactive) was used to determine metabolite changes in the plasma of SHR rats before and after yishenjiangyafang treatment in the treatment group as well as in the model and control groups. Results. After yishenjiangyafang treatment, SHRs had significant lower blood pressure. Using UPLC-Q-Exactive, we identified 26 metabolic targets of yishenjiangyafang in aged SHRs and revealed that yishenjiangyafang targeted four major metabolic pathways, linoleic acid metabolism, glycerophospholipid metabolism, arginine and proline metabolism, and steroid hormone biosynthesis. Conclusion. Yishenjiangyafang decreases the blood pressure of SHRs at least in part through targeting of four major metabolic pathways. Our study illustrates mechanisms underlying the clinical application of yishenjiangyafang in the treatment of hypertensive patients.

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