Changes of Blood Pressure Rhythm and Clock Protein Expression Levels in Spontaneously Hypertensive Rats After Ischemia-Reperfusion

Author(s):  
Jing Jin ◽  
Yumeng Liu ◽  
Jing Huang ◽  
Dong Zhang ◽  
Jian Ge ◽  
...  

Abstract Objective A variety of circadian patterns of blood pressure after ischemic stroke in patients with essential hypertension appear to be a potential risk of stroke recurrence, but the mechanism is still unclear. This study intends to reveal the changes in blood pressure rhythm and circadian clock protein expression levels in spontaneously hypertensive rats (SHR) after ischemia-reperfusion, and the relationship between the two. Methods Using the SHR middle cerebral artery occlusion experimental model, the systolic blood pressure was continuously monitored for 24 hours after the operation to observe the blood pressure rhythm. The rat tail vein blood was taken every 3h, and the serum CLOCK, BMAL1, PER1 and CRY1 protein expression levels were detected by Elisa. Pearson correlation analysis counted the relationship between SHR blood pressure rhythm and circadian clock protein fluctuation after ischemia-reperfusion. Results The proportion of abnormal blood pressure patterns in the SHR + tMCAO group was significantly higher than that in the SHR group, the serum CLOCK expression was relatively constant, and the circadian rhythm of BMAL1, PER1 and CRY1 protein expression changed significantly. Pearson analysis showed that PER1 protein level was negatively correlated with dipper (r = -0.565, P = 0.002) and extreme-dipper (r = -0.531, P = 0.001) blood pressure, and was significantly positively correlated with non-dipper blood pressure (r = 0.620, P < 0.001). Conclusion The rhythm pattern of blood pressure after ischemia-reperfusion in SHR is obviously disordered, and it is closely related to the regulation of Per1 gene.




Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 700-701
Author(s):  
Gustavo J J Silva ◽  
Edson D Moreira ◽  
Carlos E Negrao ◽  
Patricia C Brum ◽  
Eduardo M Krieger

P43 We have previously demonstrated that low-intensity exercise traning (ET) diminishes blood pressure and partially restores the sensitivity of the baroreflex bradycardia and tachycardia that are depressed in spontaneously hypertensive rats (SHR). Presently, the influence of the exercise trainig (ET) on the afferent part of the baroreflex (baroreceptor function curve) and its implication on the baroreflex was analysed in SHR and in normal control rats (NCR). NCR and SHR were subdivided in sedentary (S) and ET groups: SHR-S (n=8) and SHR-ET (n=6), and NCR-S (n=8) and NCR-ET (n=8). ET was performed on treadmill, during 60 min, 5 days/wk, at 50% of VO 2 max, for 12 wk. Arterial baroreflex sensitivity was evaluated by bradycardiac responses to phenylephrine (0.5;1;2;4;8 and 16 μg/ml, i.v.) and tachycardiac responses to sodium nitroprusside (0.5;1;2;4;8 and 16 μg/ml, i.v.). Aortic baroreceptor function curve was evaluated under pentobarbital anesthesia (40 mg/kg) during rapid variations of arterial pressure (AT/CODAS, 3kHz per channel). The relationship between changes in baroreceptor discharge (0-100%) and systolic arterial pressure was analysed using a sigmoidal regression. Mean arterial pressure was reduced in SHR-ET compared to SHR-S group (165±7 vs. 183±4 mmHg) but remained inaltared in NCR-ET compared to NCR-S (112±3 vs. 115±3 mmHg). In SHR, ET increased the sensitivity of baroreflex bradycardia (1.9±0.1 vs. 0.7±0.1 bpm.mmHg -1 ) and tachycardia (2.9±0.1 vs. 1.8±0.2 bpm.mmHg -1 ) which were depressed. In NCR-ET baroreflex bradycardia was decreased (1.4±0.1 vs. 1.7±0.1 bpm.mmHg -1 ) but baroreflex tachycardia was increased (4.6±0.5 vs. 3.0±0.2 bpm.mmHg -1 ). ET increased the aortic baroreceptor gaing-sensitivity in both groups: SHR (0.9±0.1 vs. 0.7±0.1 %.mmHg -1 ) and NCR (2.1±0.1 vs. 1.4±0.1 %.mm Hg -1 ). Conclusion:1. ET increases aortic baroreceptor gain-sensitivity in NCR as well in SHR; 2. The improvement of the baroreflex produced by ET in SHR is partially explainedd by the recovery of the baroreceptor sensitivity, which may also participate in the reduction of high blood pressure.



2012 ◽  
Vol 27 (11) ◽  
pp. 815-820 ◽  
Author(s):  
Weihong Jiang ◽  
Lihua Tan ◽  
Yunzhong Guo ◽  
Xiaogang Li ◽  
Xiaohong Tang ◽  
...  

PURPOSE: To investigate the effect of renal denervation (RDN) on the blood pressure, left ventricular hypertrophy and myocardial expression of TLR4/NF-κB in spontaneously hypertensive rats (SHR). METHODS: A total of 36 SHR were randomly assigned into control group (D0), RDN group (D) and sham group (S). 12 WKY rats of same age served as controls (WKY group). Rats in the D0 and WKY groups were sacrificed, but rats in the D and S group were sacrificed at one week and six weeks after surgery. The heart was collected and the left ventricle weighted followed by calculation of left ventricular mass index (LVMI). RESULTS: In the D0 group, the blood pressure, LVMI and protein expression of TLR4, NF-κB, TNF-α and IL-6 in the myocardium were markedly higher than that in the WKY group (p<0.05). In the D1 and D2 group, the LVMI, NE and protein expression of TLR4, NF-κB, TNF-α and IL-6 in the myocardium were significantly reduced (p<0.05). CONCLUSION: Renal denervation can significantly delay the progression of left ventricular hypertrophy in spontaneously hypertensive rats, which may be attributed to the not only the suppression of sympathetic activity and attenuation of pressure load but the improvement of myocardial immuno-inflammation.



2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Bin Zhang ◽  
Dong Li ◽  
Gexiu Liu ◽  
Wenfeng Tan ◽  
Jun Guo ◽  
...  

Objective. To investigate the effect of traditional Chinese antihypertensive compound Xinmaitong on blood pressure and vasoactive factors of vasoconstrictor endothelin-1 (ET-1) and vasodilator calcitonin gene related peptide (CGRP) in spontaneously hypertensive rats (SHRs) with early stage hypertension. Methods. Twenty male SHRs were randomly divided into two groups: 10 for hypertensive control group and 10 for hypertensive treatment group. In addition, 10 Wistar rats were used as the normal control group without any intervention. SHRs of hypertensive treatment group were orally treated with Xinmaitong, while the hypertensive control group was treated with the normal saline (NS) for a total of eight weeks. The blood pressure in SHRs was examined before and after the end of the eight-week study. After treatment, the rats were killed and the blood samples were collected to measure plasma levels of ET-1 and CGRP by ELISA method, respectively. Meanwhile, the aorta rings were isolated for measuring the mRNA expression of ET-1 and CGRP by PCR. Moreover, the protein levels of ET-1 and CGRP were studied by immunohistochemical. Results. Daily oral administration of Xinmaitong resulted in significant fall in the SHRs’ blood pressure, including systolic and diastolic blood pressures (SBP and DBP), mean blood pressure (MBP), and pulse pressure (PP). The plasma ET-1 levels were reduced and CGRP increased. In parallel, the mRNA and protein expression of ET-1 were decreased, whereas the mRNA and protein expression of CGRP were enhanced in SHRs treated with Xinmaitong. Conclusion. The present study demonstrated for the first time that Xinmaitong leads to the fall in blood pressure of SHRs and that this antihypertensive effect is, at least in part, due to improvement of arterial tone.



2012 ◽  
Vol 122 (11) ◽  
pp. 535-543 ◽  
Author(s):  
Gisele F. Bomfim ◽  
Rosangela A. Dos Santos ◽  
Maria Aparecida Oliveira ◽  
Fernanda R. Giachini ◽  
Eliana H. Akamine ◽  
...  

Activation of TLRs (Toll-like receptors) induces gene expression of proteins involved in the immune system response. TLR4 has been implicated in the development and progression of CVDs (cardio-vascular diseases). Innate and adaptive immunity contribute to hypertension-associated end-organ damage, although the mechanism by which this occurs remains unclear. In the present study, we hypothesize that inhibition of TLR4 decreases BP (blood pressure) and improves vascular contractility in resistance arteries from SHR (spontaneously hypertensive rats). TLR4 protein expression in mesenteric resistance arteries was higher in 15-week-old SHR than in age-matched Wistar controls or in 5-week-old SHR. To decrease the activation of TLR4, 15-week-old SHR and Wistar rats were treated with anti-TLR4 (anti-TLR4 antibody) or non-specific IgG control antibody for 15 days (1 μg per day, intraperitoneal). Treatment with anti-TLR4 decreased MAP (mean arterial pressure) as well as TLR4 protein expression in mesenteric resistance arteries and IL-6 (interleukin 6) serum levels from SHR when compared with SHR treated with IgG. No changes in these parameters were found in treated Wistar control rats. Mesenteric resistance arteries from anti-TLR4-treated SHR exhibited decreased maximal contractile response to NA (noradrenaline) compared with IgG-treated SHR. Inhibition of COX (cyclo-oxygenase)-1 and COX-2, enzymes related to inflammatory pathways, decreased NA responses only in mesenteric resistance arteries of SHR treated with IgG. COX-2 expression and TXA2 (thromboxane A2) release were decreased in SHR treated with anti-TLR4 compared with IgG-treated SHR. Our results suggest that TLR4 activation contributes to increased BP, low-grade inflammation and plays a role in the augmented vascular contractility displayed by SHR.



2007 ◽  
pp. 267-274 ◽  
Author(s):  
J Bešík ◽  
O Szarszoi ◽  
J Kuneš ◽  
I Netuka ◽  
J Malý ◽  
...  

Clinical and experimental studies have repeatedly indicated that overloaded hearts have a higher vulnerability to ischemia/reperfusion injury. The aim of the present study was to answer the question whether the degree of tolerance to oxygen deprivation in hearts of spontaneously hypertensive rats (SHR) may be sex-dependent. For this purpose, adult SHR and their normotensive control Wistar Kyoto (WKY) rats were used. The isolated hearts were perfused according to Langendorff at constant pressure (proportionally adjusted to the blood pressure in vivo). Recovery of contractile parameters (left ventricular systolic, diastolic and developed pressure as well as the peak rate of developed pressure) was measured during reperfusion after 20 min of global no-flow ischemia in 5 min intervals. Mean arterial blood pressure was measured by direct puncture of carotid artery under light ether anesthesia in a separate group of animals. The degree of hypertension was comparable in both sexes of SHR. The recovery of contractile functions in SHR males and females was significantly lower than in WKY rats during the whole investigated period. There was no sex difference in the recovery of WKY animals; on the other hand, the recovery was significantly better in SHR females than in SHR males. It may be concluded that the hearts of female SHR are more resistant to ischemia/reperfusion injury as compared with male SHR. This fact could have important clinical implications for the treatment of cardiovascular disease in women.





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