Bioequivalence study of four different trademarks of enalapril maleate in spontaneously hypertensive rats

INTRODUCTION: High blood pressure is a systemic disease which has major clinical and psycho-social repercussions, involves a high morbidity-mortality rate and generates high costs for the health system. Its treatment involves the use of antihypertensive drugs, which are commercialized as trademark, generic or similar drugs. PURPOSE: To verify the antihypertensive effect produced by a similar dose of different trademarks of enalapril maleate in spontaneously hypertensive rats (SHR). METHODS: Fifteen mg/kg of enalapril maleate were administered by gavage in 50 SHR rats and their blood pressure was verified through tail plethysmography every three days in a period of 16 days. RESULTS: The group treated with reference drug has shown a significant reduction on blood pressure levels when compared to the control group. Thus, treatments with enalapril maleate of generic, similar-A and similar-B brands have also shown significant reduction on animals' blood pressure. CONCLUSION: The use of generic drug and similars (A and B) drugs in the same doses and for the same period of time has not shown significant difference regarding the reference drug, which suggests that the brands tested are bioequivalent.

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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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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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Treatment with Lindera strychnifolia Reduces Blood Pressure by Decreasing Sympathetic Nerve Activity in Spontaneously Hypertensive Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x10008056 ◽

2010 ◽

Vol 38 (03) ◽

pp. 561-568 ◽

Cited By ~ 5

Author(s):

Masayuki Shimomura ◽

Hiroaki Ushikoshi ◽

Arihiro Hattori ◽

Ichijiro Murata ◽

Yasushi Ohno ◽

...

Keyword(s):

Blood Pressure ◽

Cardiac Function ◽

Systolic Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Plasma Noradrenaline ◽

Control Group ◽

Free Access ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Noradrenaline Levels

Lindera strychnifolia (Tendai-Uyaku), a medicinal plant, has long been used for the treatment of cardiac, renal and rheumatic diseases in Japan. We investigated the effect of Lindera strychnifolia on systolic blood pressure, cardiac function, and plasma noradrenaline levels in rats. Spontaneously hypertensive rats (SHR) were given free access to water or extract solution of Lindera strychnifolia, which was extracted with a ratio of 10 g Lindera strychnifolia roots/20 ml water. Systolic blood pressure was measured by using a tail-cuf sphygmomanometer twice a week from 10 to 30 weeks of age, and compared to the age-matched Wistar Kyoto rats (WKY) as a control group. At 30 weeks of age, heart function was measured by echocardiography and blood samples were taken for detection of plasma noradrenaline levels, and rats were then sacrificed. Systolic blood pressure gradually increased from 10 to 30 weeks of age in the SHR group, while it did not change in the WKY group. In the Lindera-treated SHR group, the increase in systolic blood pressure was significantly attenuated from 21 to 30 weeks of age. Echocardiography showed a significant increase in ejection fraction in the Lindera-treated SHR group (60.4 ± 7.8%) as compared to the SHR group (39.7 ± 23.4%). Plasma noradrenaline levels were significantly decreased in Lindera-treated SHR group compared to the SHR group. These results suggest that Lindera strychnifolia has an anti-hypertensive effect and improves cardiac function in spontaneous hypertensive rats. These effects may be related to the decrease in plasma noradrenaline levels by Lindera strychnifolia.

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Statistical Analysis of Homocysteine and Folate on the Regulation of Blood Pressure

Journal of Medical Imaging and Health Informatics ◽

10.1166/jmihi.2019.2793 ◽

2019 ◽

Vol 9 (8) ◽

pp. 1563-1567

Author(s):

Zhigang Huang ◽

Lin Shi ◽

Ningling Sun

Keyword(s):

Blood Pressure ◽

Statistical Analysis ◽

Spontaneously Hypertensive Rats ◽

Renal Tissue ◽

Control Group ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Weak Response ◽

Increasing Trend ◽

Regulation Of Blood Pressure

Objective: To investigate and statistically analyze homocysteine and folate on the regulation of blood pressure in spontaneously hypertensive rats (SHR), and explore whether the effect is related to angiotensin II type L receptor (AT1R) with bioinformatics. Methods: Eighteen SHRs were randomly divided into three groups: control group, methionine (Met) group and folate group (Met plus folate). Heart rate and blood pressure were monitored at different times. Serum Hcy levels were measured by ELISA kits. The expression of AT1R was detected by protein immunoblot. Results: Statistical analysis results indicated that mean arterial pressure (MAP) of the Met group at 4 and 6 weeks showed an increasing trend compared with the control group. And the Folate group at 4 weeks presented a decreasing trend compared with the Met group. The MAP of the other groups presented that great variation and no obvious trend. Serum Hcy levels were significantly increased in Met group, but decreased in folate group. AT1R protein were significantly decreased in Met and folate group. Conclusion: Hcy increased the MAP to a certain extent, and folic acid had a weak response to intervention to the effect. AT1R protein in renal tissue may not be a major effector in the pathway of elevated blood pressure.

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Effects of antiserum against alpha-rat atrial natriuretic polypeptide in spontaneously hypertensive rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.257.4.h1104 ◽

1989 ◽

Vol 257 (4) ◽

pp. H1104-H1109 ◽

Cited By ~ 1

Author(s):

A. Sasaki ◽

O. Kida ◽

T. Kita ◽

J. Kato ◽

S. Nakamura ◽

...

Keyword(s):

Blood Pressure ◽

Cardiac Output ◽

Spontaneously Hypertensive Rats ◽

Physiological Role ◽

Mean Blood Pressure ◽

Rabbit Serum ◽

Normal Rabbit Serum ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Significant Difference

To clarify the physiological role of endogenous atrial natriuretic polypeptide (ANP), we investigated the effects of specific rabbit antiserum against alpha-rat ANP (alpha-rANP) on hemodynamics, diuresis, and natriuresis in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Intravenous administration of anti-alpha-rANP antiserum caused an obvious rise of mean blood pressure and cardiac output in both SHR and WKY compared with rats administered with normal rabbit serum. Although there was no significant difference in increments of mean blood pressure between SHR and WKY, the increment of cardiac output in SHR was significantly higher than that in WKY. On the other hand, significant reductions in urine output and urinary sodium and potassium excretion lasted for approximately 20 min after administration of the antiserum in both SHR and WKY compared with rats administered with normal rabbit serum. There was no significant difference in these initial maximal decrements between SHR and WKY. These results indicate that endogenous ANP has an important physiological role in the regulation of hemodynamics and water-electrolyte balance in both SHR and WKY. The greater increment of cardiac output in SHR in response to the antiserum suggests that endogenous ANP in SHR may have a stronger cardiosuppressive action that it does in WKY.

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Auricular Acupuncture to Lower Blood Pressure Involves the Adrenal Gland in Spontaneously Hypertensive Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/3720184 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Huong Thi Mai Nguyen ◽

Der-Yen Lee ◽

Hung-Ming Wu ◽

Ching-Liang Hsieh

Keyword(s):

Blood Pressure ◽

Adrenal Gland ◽

Spontaneously Hypertensive Rats ◽

Vagal Afferents ◽

Auricular Acupuncture ◽

Control Group ◽

Hypertensive Rats ◽

Gaba A ◽

Spontaneously Hypertensive ◽

Lower Blood

Auricular acupuncture is used to treat cardiac-related diseases such as hypertension. Therefore, the purpose of the present study was to investigate the effects of auricular acupuncture on blood pressure (BP) in spontaneously hypertensive rats (SHRs). The treatment group (TG) received auricular electroacupuncture (EA) at the auricle heart (CO15) and auricle shenmen (TEF3) points. Heart rate (HR) and BP, GABA-A expression, catecholamine, and neurotransmitter levels were measured. The HR was reduced after 7 auricular EA treatments compared with controls (all p < 0.05 ). Systolic BP and diastolic BP also decreased immediately and throughout the treatments compared with controls (all p < 0.05 ). The reduction of BP and HR was reversed by bicuculline injection 30 min before auricular EA treatment (all p < 0.05 ). GABA levels in the adrenal gland were higher with auricular EA treatment compared with the control group at 4 h ( p < 0.05 ). Levels of serum noradrenaline and adrenaline were reduced at 15 min after final auricular EA treatment compared with the normal control group (both p < 0.05 ). The lowering of BP and HR by auricular EA is possibly mediated via vagal afferents from the concha to the nucleus of the solitary tract. After signal integration in the medulla oblongata, it may be transmitted through sympathetic efferent or vagal efferent or through multiple signaling pathways simultaneously to the atrionector of heart and the adrenal medulla. Further study is warranted.

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Chymase Dependent Pathway of Angiotensin II Generation and Rapeseed Derived Peptides for Antihypertensive Treatment of Spontaneously Hypertensive Rats

Frontiers in Pharmacology ◽

10.3389/fphar.2021.658805 ◽

2021 ◽

Vol 12 ◽

Author(s):

Iwona Baranowska ◽

Olga Gawrys ◽

Malwina M. Roszkowska-Chojecka ◽

Bozena Badzynska ◽

Dagmara Tymecka ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Spontaneously Hypertensive Rats ◽

Femoral Vein ◽

Control Group ◽

Hypertensive Rats ◽

Tissue Samples ◽

Spontaneously Hypertensive ◽

Young Rats ◽

The Impact

The contribution of chymase, one of the enzymes responsible for angiotensin II generation in non-ACE pathway, remains unclear in the development of hypertension. The aim of the study was to investigate chymase inhibition as potential antihypertensive therapy in spontaneously hypertensive rats (SHR). To block chymase we employed chymostatin, a commercial inhibitor, and new analogues of rapeseed-derived peptides, VWIS and RIY. These simple and easy to obtain peptides not only block chymase, but also possess weak activity to inhibit ACE. This is a first attempt to evaluate the impact of chronic administration of selected inhibitors on blood pressure of SHR in two phases of hypertension. Male SHR (6 or 16 weeks old) were treated daily for two weeks with chymostatin (CH; 2 mg/kg/day), the peptides VWIS (12.5 mg/kg/day) or RIY (7.5 mg/kg/day); control groups received chymostatin solvent (0.15% DMSO in saline) or peptide solvent (saline). The substances were administered intravenously to conscious animals via a chronically cannulated femoral vein. Systolic blood pressure (SBP) was measured by telemetry. Metabolic parameters were measured weekly, and tissue samples were harvested after two weeks of treatment. None of the administered chymase inhibitors affected the development of hypertension in young rats. Only RIY exhibited beneficial properties when administered in the established phase of hypertension: SBP decreased from 165 ± 10 to 157 ± 7 mmHg while the excretion of nitric oxide metabolites increased significantly. The glomerulosclerosis index was lower after RIY treatment in both age groups (significant only in young rats 0.29 ± 0.05 vs 0.48 ± 0.04 in the control group; p < 0.05). Hence, it seems that peptide RIY exhibits some positive effect on renal morphology. The results obtained suggest that the peptide RIY may be a useful tool in the treatment of hypertension, especially in cases when ACE inhibitors are not effective.

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Antihypertensive and Renal Protective Effects of Oryeongsan in Spontaneously Hypertensive Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/8844031 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Kiwan Kang ◽

Minjeong Jeong ◽

Hongjun Kim ◽

Beomjin Lim ◽

Sangjun Kim ◽

...

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Treated Group ◽

Renal Tissue ◽

Quality Data ◽

Protective Effects ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Significant Difference ◽

History Of Use

Oryeongsan (ORS), a traditional medicine used to regulate body fluids, has a long history of use as a diuretic in Korea, China, and Japan. ORS is commonly thought to lower blood pressure, but high-quality data on its effects are sparse. The purpose of this study was to determine the antihypertensive and renal protective effects of ORS in rats with hypertension. Spontaneously hypertensive rats (SHR) were divided into two groups with similar mean baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP). Then, 10 mL/kg of vehicle (distilled water) or 200 mg/kg of ORS extract were administered orally once a day for 3 weeks. SBP and DBP were measured at weeks 1, 2, and 3. At the end of the experiment, blood was collected, and kidneys were removed for histology. By the 2nd and 3rd week after initiation of treatment, the ORS-treated group had significantly lower SBP than control-treated rats (191.3 ± 6.5 vs. 206.3 ± 9.8 mmHg, p = 0.022 at the 2nd week; 195.8 ± 7.8 vs. 217.0 ± 8.1 mmHg, p = 0.003 at the 3rd week, respectively). The ORS-treated group trended toward having a lower DBP than control, but there was no significant difference. Blood urea nitrogen (BUN) and serum creatinine (Cr) were not different between the ORS-treated and control groups (BUN: 23.7 ± 1.1 vs. 22.7 ± 2.8 mg/dL, p = 0.508; Cr: 19.0 ± 2.2 vs. 21.6 ± 2.1 μM, p = 0.083, respectively). The percentage of renal tissue affected by tubulointerstitial fibrosis was significantly lower in the ORS-treated group (1.68 ± 0.60) compared to controls (3.17 ± 0.96, p = 0.019). These findings suggest that treatment with ORS reduces SBP and ameliorates renal damage in SHR.

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