• Title/Summary/Keyword: SHR

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Altered Cerebral Vasomotion with Decreased CGRP Level in Pial Arteries of Spontaneously Hypertensive Rats

  • Lee, Kwang-Ho;Choi, Jae-Moon;Hong, Ki-Whan
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.5
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    • pp.573-580
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    • 1998
  • The study aims to identify the mechanism (s) underlying the altered vasodilatory responses of the pial artery of spontaneously hypertensive rats (SHR) under a hypothesis that calcitonin gene-related peptide (CGRP) exerts a modulator role in the autoregulation of cerebral blood flow (CBF). The animals were divided into four groups: 1) Sprague-Dawley rats (SDR), 2) Wistar rats (WR), 3) SHR with high blood pressure $(BP{\ge}150\;mmHg),$ and 4) SHR with normotensive BP $({\le}150\;mmHg).$ The lower limit of CBF autoregulation in SHR shifted to a higher BP $(82.8{\pm}9.3\'mmHg,\;P<0.05)$ than that in SDR $(58.9{\pm}5.7\;mmHg)$. In SHR, whether the BP levels were high or normotensive, the vasodilator responses to a stepwise hypotension were significantly attenuated unlike with SDR and WR. When artificial cerebrospinal fluid (CSF) containing capsaicin $(3{\times}10^{-7}\;M)$ was suffused over the cortical surface, a transient increase in pial arterial diameter was observed in the SHR with high or normotensive BP. In contrast, SDR and WR showed a large increase in diameter, and the increase was sustained for over 10 minutes. In line with these results, the basal releases of CGRP-like immunoreactivity (CGRP-LI) in the isolated pial arteries from SHR with high and normotensive BP were $12.5{\pm}1.4\;and\;9.8{\pm}2.8\;fmole/mm^2/60\;min\;(P<0.05)$, while those from SDR and WR were $25.5{\pm}3.1\;and\;24.6{\pm}3.1\;fmole/mm^2/60\;min,$ respectively. The isolated basilar arteries showed similar results to those of the pial arteries in SHR. Thus, it is summarized that, in the SHR, the reduced autoregulatory vasodilator responses to stepwise hypotension and capsaicin may be, in part, ascribed to the decreased release of CGRP from the perivascular sensory nerve fibers of the pial arteries, and that altered vasomotor activity in SHR may not be related with the hypertensive tone.

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The Relationship between Hypertension and Central Serotonergic Nervous System Activity in Spontaneously Hypertensive Rats

  • Kim, Sung-Jin;Ko, Kwang-Ho
    • Archives of Pharmacal Research
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    • v.11 no.4
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    • pp.301-307
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    • 1988
  • Relationship between the maintenance of hypertension and central serotonergic nervous system activity in opontaneously hypertensive rats (SHR) was studied. Serotonin turnover-rates were measured in 5 brain areas as an index of serotonergic neuronal activity and compared at the ages of 14 weeks in two types of animals; (1) spontaneously hypertensive rats (SHR) (2) normotensive wistar kyoto rats (WKY). In 14-week old SHR, central serotonin turnover rate was significantly lower in telencephalon, hypothalamus/thalamus and midbrain than normotensive rat, but significantly higher in cerebellum. There were no significant differences between serotonin turnover rate in pons/medulla of SHR and that of normotensive rat. THese data suggest that the abnormally lower turnover rates of serotonin in telencephalon, hypothalamus/thalamus and midbrain may be one of the underlying neuronal factors for manifestation of hypertension in SHR.

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The Effect of Kamijaeumganghwatang(KJI) on Hypertension (가미자음강화탕(加味滋陰降火湯)이 SHR의 혈압에 미치는 영향)

  • Baek, Kyung-Min;Jo, Hyun-Kyung;Yoo, Ho-Rhyong;Kim, Yoon-Sik;Seol, In-Chan
    • The Journal of Internal Korean Medicine
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    • v.27 no.1
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    • pp.1-15
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    • 2006
  • Objective : This study was done to investigate the effect of KJT on hypertension. Methods : Spontaneous Hypertensive Rats were sensitized and challenged with Kamijaeumganghwatang(KJT) for 5 weeks. Experimental group was treated with $200mg/day/2m{\ell}$ of KJT orally and control group was treated with $2m{\ell}/day$ of normal saline instead. Results : 1. KJT significantly showed significant protection against cytotoxicity and toxicity in the liver and the kidney. 2. KJT significantly decreased the blood pressure in SHR. 3. KJT significantly decreased the levels of aldosterone in SHR. 4. KJT significantly decreased the levels of dopamine, norepinephrine and epinephrine in SHR. 5. KJT significantly decreased the levels of sodium and potassium in SHR, but it did not decrease the levels of chloride in SHR. Levels of calcium in SHR increased, but only insignificantly. 6. KJT significantly decreased the levels of IL-6 in SHR, and significantly increased the levels of IL-10 in SHR. 7. For histological effects, KJT dillated capillary vessels in the kidney, significantly decreased eosinophilic changes in heart cells, and significantly decreased endothelial damage in the aorta. Conclusion: These results suggest that KJT is useful in treatment of hypertension.

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Relationship between the regulation of blood pressure and in vivo noradrenergic neural activities in the locus coeruleus of young Spontaneously Hypertensive Rats

  • Kim, Y.T.;Lee, J.H.;Lee, E.K.;Song, M.J.;Ko, K.H.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.216-216
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    • 1996
  • The purpose of the present study was to determine whether in vivo noradrenergic neural activity in the locus coeruleus is related to the development of hypertension. Two groups of animals were prepared, 1) young spontaneously hypertensive rats (SHR) and 2) age-matched normotensive wistar kyoto rats (WKY). At il weeks of age, the release of norepinephrine (NE) and 3,4-dihydroxyphenylglycol (DOPEG) from locus coeruleus of young SHR and WKY as an index of neural activity were determined by in vivo microdialysis along with blood pressure (BP) at three conditions : 1) normal; 2) elevated BP by systemic injection of phenylephrine and 3) alpha-1 adrenoceptor stimulated by perfusion of phenylephrine into the locus coeruleus through microdialysis probe. Basal releases of NE and DOPEG from the iocus coeruleus were 0.415+/-0.089pg/20min, 1.311+/-0.293 pg/20min in SHR and 0.204+/-0.078 pg/20min, 1.492+/-0.365 pg/20min in WKY respectively. Basal release of NE from the locus coeruleus of SHR was significantly greater than that of WKY. Phenylephrine systemic injection caused elevation of BP in both SHR and WKY in a dose related manner. Following phenyephrine injection, the releases of NE and DOPEG from the locus coeruleus of SHR were significantly decreased, whereas there were no significant changes in the releases of NE and DOPEG In young WKY. Alpha-1 adrenoceptor stimulation in the locus coeruleus by perfused phenylephrine through microdialysis probe caused pressor responses in both SHR and WKY, but the magnitude of pressor response in SHR was larger compared with that in WKY. The result from the present study suggests that noradrenergic neural activity in locus coeruleus may contribute as one of triggering factors for the expression of hypertension in young SHR.

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Sulfatase 1 mediates the inhibitory effect of angiotensin II type 2 receptor inhibitor on angiotensin II-induced hypertensive mediator expression and proliferation in vascular smooth muscle cells from spontaneously hypertensive rats

  • Kim, Hye Young;Cha, Hye Ju;Kim, Hee Sun
    • Journal of Yeungnam Medical Science
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    • v.34 no.1
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    • pp.43-54
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    • 2017
  • Background: Extracellular sulfatases (Sulfs), sulfatase 1 (Sulf1) and sulfatase 2 (Sulf2), play a pivotal role in cell signaling by remodeling the 6-O-sulfation of heparan sulfate proteoglycans on the cell surface. The present study examined the effects of Sulfs on angiotensin II (Ang II)-induced hypertensive mediator expression and vascular smooth muscle cells (VSMCs) proliferation in spontaneously hypertensive rats (SHR). Methods: Ang II receptors, 12-lipoxygenase (12-LO), and endothelin-1 (ET-1) messenger RNA (mRNA) expressions in SHR VSMCs were analyzed by real-time polymerase chain reaction and Western blotting. VSMCs proliferation was determined by [$^3H$]-thymidine incorporation. Results: Basal Sulfs mRNAs expression and enzyme activity were elevated in SHR VSMCs. However, Sulfs had no effect on the basal or Ang II-induced 12-LO and ET-1 mRNA expression in SHR VSMCs. The inhibition of Ang II-induced 12-LO and ET-1 expression by blockade of the Ang II type 2 receptor ($AT_2\;R$) pathway was not observed in Sulf1 siRNA-transfected SHR VSMCs. However, Sulf2 did not affect the action of $AT_2\;R$ inhibitor on Ang II-induced 12-LO and ET-1 expression in SHR VSMCs. The down-regulation of Sulf1 induced a reduction of $AT_2\;R$ mRNA expression in SHR VSMCs. In addition, the inhibition of Ang II-induced VSMCs proliferation by blockade of the $AT_2\;R$ pathway was mediated by Sulf1 in SHR VSMCs. Conclusion: These findings suggest that extracellular sulfatase Sulf1 plays a modulatory role in the $AT_2\;R$ pathway that leads to an Ang II-induced hypertensive effects in SHR VSMCs.

Ca-dependent Alteration in Basal Tone, Basal $^{45}Ca$ Uptake and $^3H-nitrendipine$ Binding in the Aorta of Spontaneously Hypertensive Rats

  • Chang, Seok-Jong;Jeon, Byeong-Hwa;Kim, Hoe-Suk
    • The Korean Journal of Physiology
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    • v.28 no.1
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    • pp.27-35
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    • 1994
  • We investigated the alterations in basal tone of aortic strips by changing the Ca concentration, basal $^{45}Ca$ uptake and $^3H-nitrendipine$ binding of the single cells of aortic smooth muscles in the spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. While the basal tone of the aortic strips in WKY rats was not affected by alteration of Ca concentration, that in SHR was decreased by the removal of Ca from the bath solution and was recovered by the restoration of Ca to normal levels. This contraction increased in a Ca concentration-dependent manner and reached a maximum at 2 mM Ca. The basal tone of aorta in SHR was suppressed by verapamil $(10^{-6}M)$. The basal tone of aorta in SHR increased about 50% in the strips of endothelial rubbing, compared with that of intact endothelium. Basal $^{45}Ca$ uptake in the aortic single smooth muscle cells of SHR was greater than that of WKY (p<0.01), Specific bindings of $[^3H]nitrendipine$ in the aortic single smooth muscles of SHR and WKY were saturable. The dissociation constant $(K_d)\;was\;0.71{\pm}0.15\;and\;1.18{\pm}0.08nM$ SHR, respectively, and the difference in $K_d$ between two strains was statistically significant (p<0.03). The maximal binding capacity $(B_{max})\;was\;34.6{\pm}3.2\;and\;47.4{\pm}4.3\;fmol/10^6$ SHR respectively, and the difference of $(B_{max})$ between two strains was statistically significant (p<0.05). from the above results, it is suggested that the increase of Ca influx via potential-operated Ca channels and the increase of the number of dihydropyridine-sensitive Ca channels contribute to high basal tone of the aortic strips in SHR.

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ACE Inhibitory and Antihypertensive Effect of Chitosan Oligosaccharides in SHR (Chitosan 올리고당의 안지오텐신 전환효소 활성 억제 및 SHR에서의 고혈압 억제 특성)

  • Hong, Sang-Pill;Kim, Myung-Hee;Oh, Se-Wook;Han, Chan-Kyu;Kim, Yong-Hyun
    • Korean Journal of Food Science and Technology
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    • v.30 no.6
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    • pp.1476-1479
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    • 1998
  • Effect of chitosan oligosaccharides on the ACE (angiotensin I converting enzyme) inhibition and antihypertension in SHR (Spontaneously hypertensive rat) was examined. The ACE inhibition activity was observed in all the chitosan oligosaccharides used in this study, and chitosan trimer exhibited the highest inhibitory activity $(IC_{50}=0.9{\mu}M)$ compared with other chitosan oligosaccharides $(IC_{50}\;:\;2.4{\sim}100\;{\mu}M)$. The results suggested that chitosan trimer was a good inhibitor of ACE in molecular level. When the single oral dose (2.14 mg/kg, similar to dose level of Captopril, known as strong ACE inhibitor) of chitosan trimer was given to 8 or 21 week aged SHR, the blood pressure reduction of both SHRs in 4hrs were $27{\pm}4.8\;mmHg\;and\;36{\pm}4.3\;mmHg$, respectively. Therefore, it was suggested that chitosan trimer could be applicable as natural ACE inhibitor related to antihypertension.

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Effect of Estrone Treatment on Proteinuria in Maturing Lean and Obese Male SHR/Mcc-cp Rats (Estrone 투여가 SHR/Mcc-cp 계통의 정상체중과 비만한 성장기 숫쥐들에서 단백뇨 증상에 미치는 영향)

  • Park, Sonhee
    • Journal of Nutrition and Health
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    • v.23 no.6
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    • pp.451-458
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    • 1990
  • Lean and obese male spontaneously hypertensive(SHR/Mcc-cp) rats were fed a ground rat chow diet with or without 0.001% estrone added from 6 to 18 weeks of age. Urine samples were collected weekly with 24 hour fasting. Both control lean and obese rats showed significantly higher urinary protein than their estrone treated counterparts. Treatment with 0.001% estrone diet was found to reduced the proteinuria in the maturing lean and obese SHR/Mcc-cp rats. Peaks in urinary protein level were noted at 16 weeks of age in both lean and obese control rats. Both control and estrone treated lean rats showed higher proteinuria than the obese rats. Therefore, obesity does not appear to be a contributing factor to the proteinuria in young male SHR/Mcc-cp rats.

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Effect of Geumgoeshingi-Whan Pharmacopuncture on the Blood Pressure in Spontaneously Hypertensive Rats

  • Lee, Meesun;Lee, Sangmi;Jeong, Hohyn;Park, Manyong;Kim, Dong-Woung;Song, Bong-Keun;Lee, Jong-Deok;Lee, Ho Sub;Kim, Sungchul
    • Journal of Pharmacopuncture
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    • v.16 no.1
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    • pp.37-42
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    • 2013
  • Objective: The aim of this experiment was to investigate the effect and the mechanism of Geumgoeshingi-whan (GGSGW) Pharmacopuncture at the acupoint GV 4 on the blood pressure in spontaneously hypertensive rats (SHR). Methods: SHR were injected with normal saline solution (Control-SHR group)or GGSGW Pharmacopuncture (GGSGW-SHR group) at the acupoint GV 4. The systolic arterial blood pressure and renal parameters were measured for two weeks. Results: The systolic arterial blood pressure was decreased significantly after GGSGW Pharmacopuncture at the acupoint GV 4 in SHR, followed by a significant rise in creatine clearance. The plasma levels of aldosterone were decreased significantly after GGSGW Pharmacopunctureas were the plasma levels of atrial natriuretic peptide (ANP). Conclusion: These results suggest that the blood pressure was decreased significantly after GGSGW Pharmacopuncture at the acupoint GV 4 in SHR and that the depressor response of the blood pressure was related to decreases in the plasma levels of aldosterone and ANP.

Altered Cardiac $Na^{+}$,$K^{+}$-ATPase Activity in Prehypertensive Spontaneously Hypertensive Rat

  • Lee, Shin-Woong-;Lee, Jeung-Soo-
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.300-300
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    • 1994
  • $Na^{+}$,$K^{+}$-ATPase activity, $Na^{+}$-dependent phosphorylalion, and [$^3$〕ouabain binding in sarcolemma prepared from 4 week old spontaneously hypertensive rat(SHR) ventricles were compared to the same parameters in sarcolemma from age matched normotensive Wistar-Kyoto(WKY) rat ventricles to examine whether the reduced myocardial $Na^{+}$-pump activity in SHR is an inherited enzymatic defect or a second phenomenon due to sustained hypertension. The total body weights, ventricular weights, and blood pressures were the same for SHR and WKY. No significant differences in sarcolemmal protein content and protein recovery were noted between the two pups. Sarcolemma isolated from SHR ventricles showed sigificantly less $Na^{+}$,$K^{+}$-ATPase activity and number of phosphorylation sites when compared to snrcolemma 1mm the WKY ventricles. Equilibrium binding of [$^3H$〕ouabain and the turnovcr number of myocardial $Na^{+}$,$K^{+}$-ATPast however, wee the same for both groups. These results. indicate that the low affinity(${\alpha}$, or ${\alpha}_1$) isoform for ouabain is reduced in SHR compared to WKY but that the high affinity(${\alpha}$+, or ${\alpha}_2$) isoform is the same in ventricles of SHR and WKY. The reduced amount of at isoform of the $Na^{+}$,$K^{+}$-ATPasc in prehypertensive SHR ventricles may play some pole in the development of hypertension.

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