Prevention of stroke and preservation of the functions of cerebral arteries by treatment with perindopril in stroke-prone spontaneously hypertensive rats

1998 ◽  
Vol 76 (1) ◽  
pp. 26-34 ◽  
Author(s):  
H Wang ◽  
J S Smeda ◽  
RMKW Lee
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Cerebral Arteries ◽  
Subsequent Development ◽  
Treatment Withdrawal ◽  
Prolonged Treatment ◽  
Control Group ◽  
Myogenic Response ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Middle Cerebral Arteries

The aim of this study was to determine whether the prevention of stroke with perindopril treatment in stroke-prone spontaneously hypertensive rats (SHRSP) is associated with the preservation of the myogenic properties of the cerebral arteries. After weaning at 4 weeks of age, male SHRSP were fed a Japanese-style rat diet with high salt to induce stroke development. Treatment with perindopril was given by gavage every morning beginning at 6 weeks of age. There were three experimental groups: two groups treated with 4 mg ·kg-1 ·day-1 perindopril for different durations (8 or 12 weeks) and one control group consisting of littermates given distilled water. All the control animals developed stroke and died within 14 weeks of age, and myogenic response of the middle cerebral arteries (MCA) to pressure increase was lost in these animals. In contrast, all the treated SHRSP survived during the treatment period, and myogenic response of the MCA was preserved. After withdrawal of the treatment, SHRSP treated for a longer period (12 weeks) also survived longer than those treated for a shorter period (8 weeks). The subsequent development of stroke and death following treatment withdrawal after 8 or 12 weeks of treatment was associated with the loss of pressure-dependent constriction in MCA. A longer treatment duration also increased the stiffness of the MCA. MCA from SHRSP after 12 weeks of treatment had smaller external and lumen diameters, and thicker walls than those from the 8-week treatment group. In a separate study, we found that treatment of SHRSP with 1 or 4 mg ·kg-1 ·day-1 of perindopril for 24 weeks beginning at 6 weeks of age also protected them against death related to stroke, because these rats survived up to 43 weeks of age, when the experiment was terminated. We conclude that there is an association between the absence of myogenic response in cerebral arteries and stroke development in SHRSP. Perindopril treatment preserves the myogenic response of MCA in SHRSP and prevents the stroke development in these animals. A prolonged treatment could increase the survival of SHRSP through a remodelling of the MCA and increasing the stiffness of the cerebral arteries.Key words: autoregulation, myogenic response, cerebral artery, stroke, perindopril, hypertension.

Hypertension increases middle cerebral artery resting tone in spontaneously hypertensive rats: role of tonic vasoactive factor availability

2008 ◽  
Vol 114 (10) ◽  
pp. 651-659 ◽  
Author(s):  
José M. González ◽  
Beatriz Somoza ◽  
M. Victoria Conde ◽  
Maria S. Fernández-Alfonso ◽  
M. Carmen González ◽  
...  
Keyword(s):  
Cerebral Artery ◽  
Spontaneously Hypertensive Rats ◽  
Cerebral Arteries ◽  
Mesenteric Arteries ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Middle Cerebral Arteries ◽  
Myogenic Responses ◽  
Resting Tone

The present study explores the contribution of alterations in resting tone to cerebral artery narrowing in SHRs (spontaneously hypertensive rats) and the role of hypertension development. Young pre-hypertensive and adult fully hypertensive SHRs and age-matched Wistar–Kyoto rat controls were used. The contribution of basal vasoactive factors to resting tone was studied in middle cerebral arteries with pressure myography. Basal NO and O2− (superoxide anion) availability were determined with fluorescent indicators using confocal microscopy and lucigenin-enhanced chemiluminescence. Basal O2− was also assessed in mesenteric resistance arteries. Middle cerebral arteries from adult rats, but not young pre-hypertensive rats, had augmented myogenic responses and resting tone and decreased relaxation to sodium nitroprusside compared with their normotensive counterparts. Cerebral arteries from adult SHRs also had an increase in tonic NO associated with a decrease in basal O2− availability. Basal O2− was instead increased in mesenteric arteries from SHRs. The present results indicate that large cerebral arteries from SHRs have an increase in their resting tone as a consequence of sustained hypertension and that this is related to a decrease in NO responsiveness. We suggest that this increase in resting tone and myogenic responses could act as a protective mechanism against the development of stroke in SHRs. The present study also demonstrates some unusual findings regarding the current understanding of the NO/O2− balance in hypertension with important differences between vascular beds and draws attention to the complexity of this balance in cardiovascular health and disease.

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

Hypertension ◽  
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.

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

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。

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

1985 ◽  
Vol 69 (5) ◽  
pp. 511-515 ◽  
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.

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

2005 ◽  
Vol 108 (4) ◽  
pp. 349-355 ◽  
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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