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Lymphocyte intermediate-conductance Ca2+-activated K+ channel (IKCa3.1) is upregulated in spontaneously hypertensive rat
Abstracts
a single bout of dynamic exercise on a treadmill at 15 m/min for 20 min. l-nitroarginine methyl ester (L-NAME, 40 mg/kg, i.p.) significantly inhibited post exercise hypotension (25 ± 11 and 5 ± 3 mm Hg, respectively; P < 0.05). In addition, the superoxide anion generation was decreased, while the plasma nitrite production and serine phosphorylation of endothelial nitric oxide synthase were significantly elevated in spontaneously hypertensive rats at 30 min after the termination of exercise. Taken together, these data demonstrate that the increased phosphorylation of endothelial nitric oxide synthase plays a crucial role in the reduction of arterial pressure following a single bout of dynamic exercise in spontaneously hypertensive rats. doi:10.1016/j.ijcard.2009.09.228 EX000303 Lymphocyte intermediate-conductance Ca2+-activated K+ channel (IKCa3.1) is upregulated in spontaneously hypertensive rat YUANMING ZHANG, JIAN LUO, PING LIANG, LINGPENG WANG, YALOU ZHANG Department of Cardiology of the First Affiliated Hospital, Xin Jiang Medical University, China Objective: Development of hypertension has been linked to chronic low-grade inflammation. It has been shown that, in hypertension, endothelial dysfunction, subendothelial accumulation of monocytes, preactivated circulating monocytes and lymphocytes occur. Tumor necrosis factor-alpha (TNF-α ) and interleukin-6(IL-6) produced by activated inflammatory cells are mediators of inflammatory reactions. Lymphocytes express calcium-activated K+ channel encoded by IKCa3.1, the major determinants of membrane potential in lymphocytes, that are involved in cytokine secretion. The aim of the present study was to analyse the relationship between lymphocytes activation, low-grade inflammation and IKCa3.1 in spontaneously hypertensive rat. Methods: We studied spontaneously hypertensive rat (n = 10; male;) and normotensive counterpart, Wistar–Kyoto rats (n=10; male). Peripheral blood lymphocyte was obtained from spontaneously hypertensive rat and Wistar–Kyoto rats by Ficoll density gradient. Real-time PCR was used to determine express of IKCa3.1 mRNA in lymphocyte and TNF-α, IL-6 mRNA in peripheral blood derived from spontaneously hypertensive rat and Wistar–Kyoto rats. Results: The lymphocyte IKCa3.1, and TNF-α, IL-6 mRNA expressions in spontaneously hypertensive rat are elevated compared with control rats respectively. Conclusion: Inflammation plays a critical part in the pathogenesis of hypertension. The involvement of IKCa3.1 in lymphocyte activation in spontaneously hypertensive rat. IKCa3.1 may contribute to the development of hypertension. The identification of the mechanisms leading to the activation of inflammation may contribute to the development of specific therapeutic approaches to apply in hypertension. doi:10.1016/j.ijcard.2009.09.229 EX000394 Effect of D3 receptor on α-adrenergic receptor mediated proliferation of vascular smooth muscle cellsα ZHEN LI, YU HAN, DUOFEN HE, WEIBIN SHI, CHUNJIANG FU, JIAN YANG, CHUNYU ZENG Daping Hospital, The Third Military Medical University, China Objective: To determine the effect of D3 receptor on α-adrenergic receptor-mediated proliferation of vascular smooth muscle (VSMC) cells. Methods: The primary cultured VSMC cells were treated by norepinephrine (NE) with or without the presence of D3 receptor agonist, PD128907.
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The proliferation of VSMC cells was determined by [3H]-TdR incorporation. Result: NE dose-dependently increased proliferation of primary cultured VSMC cells from aorta of Sprague–Dawley rats, this effect was via α-adrenergic receptor, because α-adrenergic receptor blocker, phentolamine, blocked the stimulatory effect of NE on VSMC proliferation. D3 receptor agonist, PD128907, by itself (10− 8 mol/L or 10− 7 mol/L) had no effect, but reduced the stimulatory effect of NE on VSMC proliferation [NE10−6 mol/L=6315±245 cpm vs. NE10−6 mol/L+PD128907 10−8 mol/ L = 5047 ±331 cpm, P < 0.05; NE10− 6 mol/L= 6315 ±>245 cpm vs. NE10− 6 mol/L+PD128907 10− 7 mol/L = 4898 ± 286 cpm, P < 0.05]. Conclusion: Activation of D3 receptor reduces the stimulatory effect of NE on VSMC proliferation, which may take part into the pathogenesis of essential hypertension. doi:10.1016/j.ijcard.2009.09.230 EX000442 Protection of retinal vasculature by losartan against apoptosis and vasculopathy in rats with spontaneous hypertension DEYE YANG, MINGYIN ZHANG, XIAOYAN HUANG, FEI FANG, BIXIN CHEN, SAIBIN WANG, XIANGXIANG SHI The First Affiliated Hospital, China Objectives: Retinal blood vessels may develop vasculopathy and apoptosis in response to hypertension. This study was aimed at testing the role of losartan, a specific antagonist of AT1 receptor in regulation of vascular apoptosis in retinal vasculature with hypertension. Design and methods: Losartan potassium was administered to spontaneously hypertensive rats (SHR). Blood pressure was measured in SHR as well as normotensive Wistar–Kyoto rats (WKY). Eye fundus was examined in alive animals and then tissue specimens collected for histochemistry by hematoxylin and eosin staining, terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL), immunohistochemistry, and transmission electron microscopy. Results: Losartan treatment for 4– 8 weeks reduced blood pressure of SHR to the normal levels seen in WKY. The losartan-treated SHR showed marked improvement of retinal vascular morphology when compared to untreated SHR. The retinal blood networks of the treated SHR developed lower degrees of vasculopathy and apoptosis. TUNEL and transmission electron microscopy also revealed that losartan exerted its protective effects not only on endothelial cells but on pericytes as well. The blood vessels of losartantreated animals also showed decreased expression of bax with elevation of bcl-2. Conclusions: Treatment with losartan, a medicine that lowers blood pressure by blocking AT1 receptor, can protect the retinal vasculature against the injury by hypertension by inhibiting apoptosis of vascular cells apoptosis and by preventing hypertensive retinopathy. doi:10.1016/j.ijcard.2009.09.231 EX000443 Reduced expression of FXYD domain containing ion transport regulator 5 (FXYD5) in hypertension DEYE YANG, FEI FANG, CHANGXI CHEN, XIAOWANG LI, XIAOYAN HUANG, XIANGXIANG SHI, DANDAN LAI The First Affiliated Hospital, China Objectives: Hypertension involves a complicated interaction between environmental and genetic factors. In a DNA microarray analysis, we studied the expression of genes related to hypertension in spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto (WKY) rats. Design and methods: Using a DNA microarray chip and reverse transcriptase-PCR (RT-PCR), we compared changes in gene expression in the second-order mesenteric arteries and kidneys of male
a single bout of dynamic exercise on a treadmill at 15 m/min for 20 min. l-nitroarginine methyl ester (L-NAME, 40 mg/kg, i.p.) significantly inhibited post exercise hypotension (25 ± 11 and 5 ± 3 mm Hg, respectively; P < 0.05). In addition, the superoxide anion generation was decreased, while the plasma nitrite production and serine phosphorylation of endothelial nitric oxide synthase were significantly elevated in spontaneously hypertensive rats at 30 min after the termination of exercise. Taken together, these data demonstrate that the increased phosphorylation of endothelial nitric oxide synthase plays a crucial role in the reduction of arterial pressure following a single bout of dynamic exercise in spontaneously hypertensive rats. doi:10.1016/j.ijcard.2009.09.228 EX000303 Lymphocyte intermediate-conductance Ca2+-activated K+ channel (IKCa3.1) is upregulated in spontaneously hypertensive rat YUANMING ZHANG, JIAN LUO, PING LIANG, LINGPENG WANG, YALOU ZHANG Department of Cardiology of the First Affiliated Hospital, Xin Jiang Medical University, China Objective: Development of hypertension has been linked to chronic low-grade inflammation. It has been shown that, in hypertension, endothelial dysfunction, subendothelial accumulation of monocytes, preactivated circulating monocytes and lymphocytes occur. Tumor necrosis factor-alpha (TNF-α ) and interleukin-6(IL-6) produced by activated inflammatory cells are mediators of inflammatory reactions. Lymphocytes express calcium-activated K+ channel encoded by IKCa3.1, the major determinants of membrane potential in lymphocytes, that are involved in cytokine secretion. The aim of the present study was to analyse the relationship between lymphocytes activation, low-grade inflammation and IKCa3.1 in spontaneously hypertensive rat. Methods: We studied spontaneously hypertensive rat (n = 10; male;) and normotensive counterpart, Wistar–Kyoto rats (n=10; male). Peripheral blood lymphocyte was obtained from spontaneously hypertensive rat and Wistar–Kyoto rats by Ficoll density gradient. Real-time PCR was used to determine express of IKCa3.1 mRNA in lymphocyte and TNF-α, IL-6 mRNA in peripheral blood derived from spontaneously hypertensive rat and Wistar–Kyoto rats. Results: The lymphocyte IKCa3.1, and TNF-α, IL-6 mRNA expressions in spontaneously hypertensive rat are elevated compared with control rats respectively. Conclusion: Inflammation plays a critical part in the pathogenesis of hypertension. The involvement of IKCa3.1 in lymphocyte activation in spontaneously hypertensive rat. IKCa3.1 may contribute to the development of hypertension. The identification of the mechanisms leading to the activation of inflammation may contribute to the development of specific therapeutic approaches to apply in hypertension. doi:10.1016/j.ijcard.2009.09.229 EX000394 Effect of D3 receptor on α-adrenergic receptor mediated proliferation of vascular smooth muscle cellsα ZHEN LI, YU HAN, DUOFEN HE, WEIBIN SHI, CHUNJIANG FU, JIAN YANG, CHUNYU ZENG Daping Hospital, The Third Military Medical University, China Objective: To determine the effect of D3 receptor on α-adrenergic receptor-mediated proliferation of vascular smooth muscle (VSMC) cells. Methods: The primary cultured VSMC cells were treated by norepinephrine (NE) with or without the presence of D3 receptor agonist, PD128907.
S69
The proliferation of VSMC cells was determined by [3H]-TdR incorporation. Result: NE dose-dependently increased proliferation of primary cultured VSMC cells from aorta of Sprague–Dawley rats, this effect was via α-adrenergic receptor, because α-adrenergic receptor blocker, phentolamine, blocked the stimulatory effect of NE on VSMC proliferation. D3 receptor agonist, PD128907, by itself (10− 8 mol/L or 10− 7 mol/L) had no effect, but reduced the stimulatory effect of NE on VSMC proliferation [NE10−6 mol/L=6315±245 cpm vs. NE10−6 mol/L+PD128907 10−8 mol/ L = 5047 ±331 cpm, P < 0.05; NE10− 6 mol/L= 6315 ±>245 cpm vs. NE10− 6 mol/L+PD128907 10− 7 mol/L = 4898 ± 286 cpm, P < 0.05]. Conclusion: Activation of D3 receptor reduces the stimulatory effect of NE on VSMC proliferation, which may take part into the pathogenesis of essential hypertension. doi:10.1016/j.ijcard.2009.09.230 EX000442 Protection of retinal vasculature by losartan against apoptosis and vasculopathy in rats with spontaneous hypertension DEYE YANG, MINGYIN ZHANG, XIAOYAN HUANG, FEI FANG, BIXIN CHEN, SAIBIN WANG, XIANGXIANG SHI The First Affiliated Hospital, China Objectives: Retinal blood vessels may develop vasculopathy and apoptosis in response to hypertension. This study was aimed at testing the role of losartan, a specific antagonist of AT1 receptor in regulation of vascular apoptosis in retinal vasculature with hypertension. Design and methods: Losartan potassium was administered to spontaneously hypertensive rats (SHR). Blood pressure was measured in SHR as well as normotensive Wistar–Kyoto rats (WKY). Eye fundus was examined in alive animals and then tissue specimens collected for histochemistry by hematoxylin and eosin staining, terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL), immunohistochemistry, and transmission electron microscopy. Results: Losartan treatment for 4– 8 weeks reduced blood pressure of SHR to the normal levels seen in WKY. The losartan-treated SHR showed marked improvement of retinal vascular morphology when compared to untreated SHR. The retinal blood networks of the treated SHR developed lower degrees of vasculopathy and apoptosis. TUNEL and transmission electron microscopy also revealed that losartan exerted its protective effects not only on endothelial cells but on pericytes as well. The blood vessels of losartantreated animals also showed decreased expression of bax with elevation of bcl-2. Conclusions: Treatment with losartan, a medicine that lowers blood pressure by blocking AT1 receptor, can protect the retinal vasculature against the injury by hypertension by inhibiting apoptosis of vascular cells apoptosis and by preventing hypertensive retinopathy. doi:10.1016/j.ijcard.2009.09.231 EX000443 Reduced expression of FXYD domain containing ion transport regulator 5 (FXYD5) in hypertension DEYE YANG, FEI FANG, CHANGXI CHEN, XIAOWANG LI, XIAOYAN HUANG, XIANGXIANG SHI, DANDAN LAI The First Affiliated Hospital, China Objectives: Hypertension involves a complicated interaction between environmental and genetic factors. In a DNA microarray analysis, we studied the expression of genes related to hypertension in spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto (WKY) rats. Design and methods: Using a DNA microarray chip and reverse transcriptase-PCR (RT-PCR), we compared changes in gene expression in the second-order mesenteric arteries and kidneys of male