Hypertension: Journal of the American Heart Association最新文献_第2页

AT1 Receptor Blockade Reduces Cardiac Calcineurin Activity in Hypertensive Rats AT1受体阻断降低高血压大鼠心脏钙调磷酸酶活性

Hypertension: Journal of the American Heart Association Pub Date : 2002-08-01 DOI: 10.1161/01.HYP.0000026668.50222.1E

K. Nagata, F. Somura, K. Obata, M. Odashima, H. Izawa, S. Ichihara, T. Nagasaka, M. Iwase, Yoshiji Yamada, N. Nakashima, M. Yokota

{"title":"AT1 Receptor Blockade Reduces Cardiac Calcineurin Activity in Hypertensive Rats","authors":"K. Nagata, F. Somura, K. Obata, M. Odashima, H. Izawa, S. Ichihara, T. Nagasaka, M. Iwase, Yoshiji Yamada, N. Nakashima, M. Yokota","doi":"10.1161/01.HYP.0000026668.50222.1E","DOIUrl":"https://doi.org/10.1161/01.HYP.0000026668.50222.1E","url":null,"abstract":"The possible role of calcineurin in the attenuation of cardiac hypertrophy and fibrosis by blockade of the angiotensin II type 1 (AT1) receptor was investigated in Dahl salt-sensitive (DS) rats. The effect of the calcineurin inhibitor FK506 was also studied. DS rats progressively developed severe hypertension when fed a diet containing 8% NaCl from 7 weeks of age. In addition, marked cardiac hypertrophy and fibrosis were apparent and the activity of calcineurin and its mRNA expression in the myocardium was increased in these animals at 12 weeks in comparison with age-matched Dahl salt-resistant rats. The abundance of angiotensin-converting enzyme (ACE) and transforming growth factor (TGF)-&bgr;1 mRNAs was also increased in the hearts of DS rats at 12 weeks. Treatment of DS rats with a non-antihypertensive dose of the selective AT1 receptor blocker candesartan (1 mg/kg per day) or FK506 (0.1 mg/kg per day) from 7 to 12 weeks attenuated both calcineurin activity and its mRNA expression in the heart, as well as the development of cardiac hypertrophy and fibrosis, without affecting cardiac function. Treatment with candesartan, but not FK506, prevented the upregulation of ACE and TGF-&bgr;1 gene expression. Both candesartan and FK506 prevented the load-induced induction of fetal-type cardiac genes. These results demonstrate that AT1 receptor blockade attenuates the development of cardiac hypertrophy and fibrosis as well as the activation of calcineurin, without an antihypertensive effect, in rats with salt-sensitive hypertension. Calcineurin may be downstream from TGF-&bgr;1 in AT1 receptor-mediated angiotensin II signaling in vivo.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"32 1","pages":"168-174"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90228726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 102

Decrease in Renal Medullary Endothelial Nitric Oxide Synthase of Fructose-Fed, Salt-Sensitive Hypertensive Rats 果糖喂养的盐敏感高血压大鼠肾髓质内皮一氧化氮合酶的降低

Hypertension: Journal of the American Heart Association Pub Date : 2002-08-01 DOI: 10.1161/01.HYP.0000024267.71656.0D

Y. Nishimoto, T. Tomida, H. Matsui, Takayuki Ito, K. Okumura

{"title":"Decrease in Renal Medullary Endothelial Nitric Oxide Synthase of Fructose-Fed, Salt-Sensitive Hypertensive Rats","authors":"Y. Nishimoto, T. Tomida, H. Matsui, Takayuki Ito, K. Okumura","doi":"10.1161/01.HYP.0000024267.71656.0D","DOIUrl":"https://doi.org/10.1161/01.HYP.0000024267.71656.0D","url":null,"abstract":"We investigated the expression of endothelial NO synthase (eNOS) in the kidneys of fructose-fed insulin-resistant rats (FFR) with a low- or high-sodium diet. Male Sprague-Dawley rats were fed a control (C) or high-fructose (40% fructose; F) diet, with each coming in low-sodium (0.024% NaCl; LS-C or LS-F) or high-sodium (3% NaCl; HS-C or HS-F) varieties, for 2 weeks. Half of the FFR were orally administered pioglitazone (10 mg · kg−1 · day−1), an insulin-sensitizing agent (LS-FP or HS-FP). The systolic blood pressure was significantly higher in the HS-F rats than in the LS-F rats or the HS-C rats (HS-F rats, 129±4 mm Hg, versus LS-F rats, 115±3 mm Hg, P <0.05; or versus HS-C rats, 116±5 mm Hg, P <0.05), which indicated the salt dependence of hypertension in FFR. The protein expression of eNOS in the renal medulla of FFR was significantly lower than that in control rats during a high sodium load. The administration of pioglitazone prevented the hypertension (HS-F rats, 129±4 mm Hg, versus HS-FP rats, 113±3 mm Hg, P <0.05) and the reduction of medullary eNOS protein expression in HS-F rats. There was no significant difference in eNOS expression in the renal cortex or aorta between FFR and control rats, regardless of sodium load. These results suggest that the decrease in renal medullary NO production by eNOS during a high sodium load may play a role in fructose-fed, salt-sensitive hypertension.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"11 1","pages":"190-194"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75211459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 62

Renal Perfusion in Blacks: Alterations Caused by Insuppressibility of Intrarenal Renin With Salt 黑人肾灌注:盐对肾内肾素无抑制作用引起的改变

Hypertension: Journal of the American Heart Association Pub Date : 2002-08-01 DOI: 10.1161/01.HYP.0000024349.85680.87

D. A. Price, N. Fisher, M. Lansang, R. Stevanovic, G. Williams, N. Hollenberg

{"title":"Renal Perfusion in Blacks: Alterations Caused by Insuppressibility of Intrarenal Renin With Salt","authors":"D. A. Price, N. Fisher, M. Lansang, R. Stevanovic, G. Williams, N. Hollenberg","doi":"10.1161/01.HYP.0000024349.85680.87","DOIUrl":"https://doi.org/10.1161/01.HYP.0000024349.85680.87","url":null,"abstract":"We have reported that an increased intrarenal renin-angiotensin system activity may be responsible for the reduction in renal plasma flow (RPF) in apparently healthy blacks in comparison to healthy whites during high salt balance. To ascertain whether these differences only exist in the high salt state, we performed the following study, concentrating on the manipulation of the renin system during low salt intake. We measured in 19 healthy blacks and 22 healthy whites para-aminohippurate and inulin clearances as an indication of RPF and glomerular filtration rate, respectively, on both high (200 mmol/d) and low (10 mmol/d) salt balance in random order. A subset of 11 blacks and 12 whites additionally received an angiotensin II infusion while in low salt balance (3 ng/kg per minute for 45 minutes) and captopril to assess differences in RPF response to a converting enzyme inhibitor. The 19 whites had significantly higher RPF when compared with blacks (P =0.033) when studied on high salt. However, during low salt balance, the RPFs were comparable in the 2 groups. Plasma renin activity was similar in the 2 groups on both diets. In the subset that received angiotensin II and captopril while in low salt balance, the renal vascular response was not different in whites and blacks. These data provide additional support for the concept that the intrarenal tissue renin system is more active in blacks than whites on a typical (high salt) diet and that the difference reflects primarily incomplete tissue renin suppression with an increase in salt intake. The mechanism involved may contribute to the increased susceptibility to renal injury in blacks.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"11 1","pages":"186-189"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85373959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 62

Effects of Black Race on Forearm Resistance Vessel Function 黑人对前臂阻力血管功能的影响

Hypertension: Journal of the American Heart Association Pub Date : 2002-08-01 DOI: 10.1161/01.HYP.0000024571.69634.ED

David F Kahn, S. Duffy, Douglas Tomasian, M. Holbrook, Lynn Rescorl, Judson D. Russell, N. Gokce, J. Loscalzo, J. Vita

{"title":"Effects of Black Race on Forearm Resistance Vessel Function","authors":"David F Kahn, S. Duffy, Douglas Tomasian, M. Holbrook, Lynn Rescorl, Judson D. Russell, N. Gokce, J. Loscalzo, J. Vita","doi":"10.1161/01.HYP.0000024571.69634.ED","DOIUrl":"https://doi.org/10.1161/01.HYP.0000024571.69634.ED","url":null,"abstract":"Presentation, response to therapy, and clinical outcome in hypertension differ according to race, and these observations could relate to differences in microvascular function. We examined forearm microvascular function in age-matched black (n=56) and white subjects (n=62) using intra-arterial agonist infusion and venous occlusion plethysmography. In normotensive subjects (n=70; 34 black and 36 white normotensives), methacholine-, sodium nitroprusside-, and verapamil-induced vasodilation was equivalent in black and white subjects. In hypertensive subjects (n=48; 22 black and 26 white hypertensives), the vasodilator response to methacholine was markedly lower in black subjects compared with white subjects (P <0.001). The vasodilator responses to sodium nitroprusside and verapamil, however, were equivalent in black and white hypertensive subjects. Acute ascorbic acid infusion improved the methacholine response equally in black and white hypertensive patients, suggesting that a difference in a rapidly reversible form of oxidative stress does not explain these findings. Thus, the present study demonstrates important racial differences in vascular function and a marked impairment in endothelial vasomotor function in black patients with hypertension. Further studies will be required to elucidate the mechanisms and determine whether these insights will lead to more appropriately tailored management of hypertension and its complications.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"131 2 1","pages":"195-201"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79246028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 93

Upregulation of L-Type Ca2+ Channels in Mesenteric and Skeletal Arteries of SHR SHR患者肠系膜和骨骼动脉中l型Ca2+通道的上调

Hypertension: Journal of the American Heart Association Pub Date : 2002-08-01 DOI: 10.1161/01.HYP.0000025877.23309.36

P. Pratt, S. Bonnet, L. M. Ludwig, P. Bonnet, N. Rusch

{"title":"Upregulation of L-Type Ca2+ Channels in Mesenteric and Skeletal Arteries of SHR","authors":"P. Pratt, S. Bonnet, L. M. Ludwig, P. Bonnet, N. Rusch","doi":"10.1161/01.HYP.0000025877.23309.36","DOIUrl":"https://doi.org/10.1161/01.HYP.0000025877.23309.36","url":null,"abstract":"An increased Ca2+ influx attributed to dihydropyridine-sensitive L-type Ca2+ channels has been demonstrated in mesenteric vascular smooth muscle cells of spontaneously hypertensive rats (SHR). This study examined whether an upregulation of the pore-forming &agr;1C subunit of the L-type Ca2+ channel underlies this ionic defect. With the use of mesenteric arcade arteries from 12- to 16-week-old SHR and normotensive Wistar Kyoto (WKY) rats, reverse transcriptase–polymerase chain reaction demonstrated an increased level of amplified cDNA corresponding to the &agr;1C subunit mRNA in the SHR arteries. Western blots confirmed that the increased mRNA expression was associated with a 3.4-fold increase in the immunoreactive signal of the &agr;1C subunit protein in SHR compared with WKY mesenteric arteries, and immunocytochemistry confirmed this abnormality at the single-cell level. Finally, isolated mesenteric arteries from SHR were highly reactive to Bay K8644 and developed anomalous Ca2+-dependent tone, suggesting a functional role for &agr;1C subunit upregulation in vascular hyperreactivity. To determine if these Ca2+ channel abnormalities extended to the SHR skeletal muscle bed, we repeated a similar series of studies in WKY and SHR hind limb arteries. Skeletal muscle arteries from SHR also expressed higher levels of &agr;1C subunit mRNA and protein than WKY arteries and developed anomalous Ca2+-dependent tone attributed to L-type Ca2+ channels. Our data provide the first evidence that the &agr;1C subunit mRNA and protein are upregulated in SHR arteries and that the increased numbers of L-type Ca2+ channel pores are associated with the generation of abnormal vascular tone.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"1 1","pages":"214-219"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79376544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 126

Efficacy of Eplerenone Added to Renin-Angiotensin Blockade in Hypertensive Patients 肾素-血管紧张素阻滞剂联合依普利酮治疗高血压的疗效观察

Hypertension: Journal of the American Heart Association Pub Date : 2002-08-01 DOI: 10.1161/01.HYP.0000025146.19104.FE

H. Krum, H. Nolly, D. Workman, Weizhong He, B. Roniker, S. Krause, Kaffa Fakouhi

{"title":"Efficacy of Eplerenone Added to Renin-Angiotensin Blockade in Hypertensive Patients","authors":"H. Krum, H. Nolly, D. Workman, Weizhong He, B. Roniker, S. Krause, Kaffa Fakouhi","doi":"10.1161/01.HYP.0000025146.19104.FE","DOIUrl":"https://doi.org/10.1161/01.HYP.0000025146.19104.FE","url":null,"abstract":"The efficacy and tolerability of eplerenone, a selective aldosterone blocker, was assessed when added to existing antihypertensive therapy with an ACE inhibitor or an angiotensin II receptor blocker (ARB). Hypertensive patients (n=341) whose blood pressure (BP) was not controlled despite ACE inhibitor or ARB were randomized (double-blind) to receive 50 mg eplerenone (increasing to 100 mg if required) once daily or placebo for 8 weeks. Diastolic and systolic BP and adverse events were recorded. By study end (week 8), mean seated diastolic BP was significantly reduced from week 0 among patients receiving eplerenone/ARB (−12.7±0.81 mm Hg) compared with those receiving placebo/ARB (−9.3±0.83 mm Hg). The change in mean seated diastolic BP was −9.9±0.88 mm Hg in eplerenone/ACE inhibitor patients and −8.0±0.86 mm Hg in placebo/ACE inhibitor patients (P =NS). Systolic BP levels were also significantly lower at week 8 for eplerenone/ACE inhibitor (−13.4±1.35 mm Hg) and eplerenone/ARB (−16.0±1.37 mm Hg) patients, respectively, compared with placebo/ACE inhibitor (−7.5±1.31 mm Hg) and placebo/ARB patients (−9.2±1.41 mm Hg). Adverse events were generally nonsevere and not significantly different between eplerenone and placebo. This study demonstrated that in patients whose BP was not controlled with an ACE inhibitor or ARB, the addition of eplerenone over an 8-week period significantly lowered systolic BP in both groups and diastolic BP in ARB patients. Selective aldosterone blockade with eplerenone, therefore, may be useful add-on therapy in hypertensive patients inadequately controlled on ACE inhibitor or ARB alone.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"140 1","pages":"117-123"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88741948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 225

Heart Rate Variability and Baroreflex Function in AT2 Receptor-Disrupted Mice AT2受体紊乱小鼠的心率变异性和压力反射功能

Hypertension: Journal of the American Heart Association Pub Date : 2002-08-01 DOI: 10.1161/01.HYP.0000027279.69240.75

V. Gross, R. Plehm, J. Tank, J. Jordan, A. Diedrich, M. Obst, F. Luft

{"title":"Heart Rate Variability and Baroreflex Function in AT2 Receptor-Disrupted Mice","authors":"V. Gross, R. Plehm, J. Tank, J. Jordan, A. Diedrich, M. Obst, F. Luft","doi":"10.1161/01.HYP.0000027279.69240.75","DOIUrl":"https://doi.org/10.1161/01.HYP.0000027279.69240.75","url":null,"abstract":"We adapted telemetry and sequence analysis employed in humans to mice and measured heart rate variability and the spontaneous baroreflex sensitivity in angiotensin II type 2 (AT2) receptor–deleted (AT2 −/−) and wild-type (AT2 +/+) mice with either deoxycorticosterone acetate (DOCA)-salt hypertension or N&ohgr;-nitro-l-arginine methylester hydrochloride (L-NAME) hypertension. Mean arterial pressure leveled during the day at 101±1 mm Hg and during the night at 109±1 mm Hg in AT2 receptor–deleted mice, compared with 98±2 mm Hg (day) and 104±2 mm Hg (night) in wild-type mice. Mean arterial pressure increased in AT2 receptor–deleted mice with L-NAME to 114±1 mm Hg (day) and 121±1 mm Hg (night), compared with 105±2 mm Hg (day) and 111±2 mm Hg (night), respectively. DOCA-salt also increased day and night blood pressures in AT2 receptor–deleted mice to a greater degree than in wild-type mice. Heart rate variability in the time and frequency domain was not different between AT2 receptor–deleted mice and AT2 receptor–deleted mice at baseline. Systolic blood pressure variability in the low frequency band was lower in AT2 receptor–deleted mice (0.6±0.1 ms2 versus 3.9±1.3 ms2) than in wild-type mice. Baroreceptor-heart rate reflex sensitivity was significantly increased in AT2 receptor–deleted mice compared with wild-type mice (3.4±0.6 versus 2.1±0.5 ms/mm Hg). These differences remained after DOCA-salt and L-NAME treatments. We conclude that activation of the AT2 receptor impairs arterial baroreceptor reflex function, probably by a central action. These data support the existence of an inhibitory central effect of the AT2 receptor on baroreflex function.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"9 1","pages":"207-213"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82046924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 46

Rapid Effects of Aldosterone and Spironolactone in the Isolated Working Rat Heart 醛固酮和螺内酯对离体工作大鼠心脏的快速作用

Hypertension: Journal of the American Heart Association Pub Date : 2002-08-01 DOI: 10.1161/01.HYP.0000025879.29822.24

J. Barbato, P. Mulrow, J. Shapiro, R. Franco‐Saenz

{"title":"Rapid Effects of Aldosterone and Spironolactone in the Isolated Working Rat Heart","authors":"J. Barbato, P. Mulrow, J. Shapiro, R. Franco‐Saenz","doi":"10.1161/01.HYP.0000025879.29822.24","DOIUrl":"https://doi.org/10.1161/01.HYP.0000025879.29822.24","url":null,"abstract":"Chronic administration of aldosterone promotes myocardial fibrosis in rats. The Randomized Aldactone Evaluation Study reported that the aldosterone antagonist spironolactone improved outcome in patients with congestive heart failure, suggesting a deleterious effect of aldosterone in the heart. Aldosterone has been shown to have rapid nongenomic effects in different tissues including the heart. However, the hemodynamic actions of aldosterone and spironolactone are not well characterized. In this study, we examined the hemodynamic effects of aldosterone and its receptor antagonist, spironolactone, in the isolated rat heart by use of the Langendorff-Neely technique. Perfusion with 10 nmol/L aldosterone increased contractility by 45% within 2 to 4 minutes (P <0.01). Similar to the aldosterone effect, 10 nmol/L spironolactone increased contractility by 41% (P <0.01). Furthermore, 100-fold molar excess of spironolactone did not block the aldosterone effect. Perfusion of aldosterone plus spironolactone resulted in the highest increase in contractility 106% (P <0.01). The threshold response for aldosterone occurred within physiological concentrations (0.5 to 1 nmol/L), and maximal contractility was achieved with 10 nmol/L aldosterone. For spironolactone, the threshold and maximal contractile responses occurred at concentrations readily achieved with clinical dosing, 0.1 to 0.5 nmol/L and 1.0 nmol/L, respectively. These data demonstrate that aldosterone and spironolactone have rapid, positive inotropic actions on the myocardium. Moreover, addition of spironolactone to aldosterone increased contractility beyond the maximal responses elicited by each agent when perfused alone, thus suggesting different pathways of action. Furthermore, the intrinsic inotropic effects of spironolactone might be relevant to the apparent beneficial effect this compound has in patients with congestive heart failure.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"7 1","pages":"130-135"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89622474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 64

Angiogenesis and Antifibrotic Action by Hepatocyte Growth Factor in Cardiomyopathy 肝细胞生长因子在心肌病中的血管生成和抗纤维化作用

Hypertension: Journal of the American Heart Association Pub Date : 2002-07-01 DOI: 10.1161/01.HYP.0000020755.56955.BF

Y. Taniyama, R. Morishita, M. Aoki, K. Hiraoka, K. Yamasaki, N. Hashiya, Kunio Matsumoto, Toshikazu Nakamura, Y. Kaneda, T. Ogihara

{"title":"Angiogenesis and Antifibrotic Action by Hepatocyte Growth Factor in Cardiomyopathy","authors":"Y. Taniyama, R. Morishita, M. Aoki, K. Hiraoka, K. Yamasaki, N. Hashiya, Kunio Matsumoto, Toshikazu Nakamura, Y. Kaneda, T. Ogihara","doi":"10.1161/01.HYP.0000020755.56955.BF","DOIUrl":"https://doi.org/10.1161/01.HYP.0000020755.56955.BF","url":null,"abstract":"Impairment of cardiac function in cardiomyopathy has been postulated to be related to decreased blood blow and increased collagen synthesis. Therefore, a therapeutic approach to alter the blood flow or fibrosis directly by means of growth factors may open a new therapeutic concept in dilated cardiomyopathy. From this viewpoint, hepatocyte growth factor (HGF) is a unique growth factor with antifibrosis and angiogenesis effects. Using the hereditary cardiomyopathic Syrian hamster as a model of genetically determined cardiomyopathy and heart failure, the effects of overexpression of HGF on fibrosis and microvascular dysfunction were examined. HGF gene or control vector was injected by the Hemagglutinating Virus of Japan–liposome method into the anterior heart of cardiomyopathic hamsters (Bio 14.6) under echocardiography once a week, from 12 to 20 weeks of age (total, 8 times). Blood flow, as assessed by a laser Doppler imager score, and the capillary density in hearts, as assessed by alkaline phosphatase staining, were significantly increased in hamsters transfected with HGF gene compared with control-vector-transfected hamsters (P <0.01). In contrast, the fibrotic area was significantly decreased in hamsters transfected with HGF gene compared with control (P <0.01). Overall, in vivo experiments demonstrated that transfection of HGF gene into the myocardium of cardiomyopathic hamsters stimulated blood flow through the induction of angiogenesis and reduction of fibrosis. These results suggest that HGF gene transfer may be useful to protect against myocardial injury in cardiomyopathy through its cardioprotective effects such as antifibrosis and angiogenesis actions.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"3 1","pages":"47-53"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85505644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 125

Chamber-Dependent Expression of Brain Natriuretic Peptide and Its mRNA in Normal and Diabetic Pig Heart 正常和糖尿病猪心脏中脑利钠肽及其mRNA的室依赖性表达

Hypertension: Journal of the American Heart Association Pub Date : 2002-07-01 DOI: 10.1161/01.HYP.0000021780.21830.DD

C. Christoffersen, J. Goetze, E. Bartels, M. Larsen, U. Ribel, J. Rehfeld, B. Rolin, L. Nielsen

{"title":"Chamber-Dependent Expression of Brain Natriuretic Peptide and Its mRNA in Normal and Diabetic Pig Heart","authors":"C. Christoffersen, J. Goetze, E. Bartels, M. Larsen, U. Ribel, J. Rehfeld, B. Rolin, L. Nielsen","doi":"10.1161/01.HYP.0000021780.21830.DD","DOIUrl":"https://doi.org/10.1161/01.HYP.0000021780.21830.DD","url":null,"abstract":"Brain natriuretic peptide (BNP) is produced in cardiac myocytes, and increased secretion is closely associated with cardiac dysfunction. However, several fundamental aspects of BNP expression in the myocardium have not yet been resolved. In the present study, we report the presence of a precursor BNP mRNA transcript and a mature BNP mRNA transcript in normal porcine hearts. In normal pigs, the amount of precursor BNP mRNA was similar in atrial and ventricular myocardium, whereas the mature BNP transcript was 10- to 50-fold more abundant in atrial than in ventricular myocardium. Quantitation of proBNP in normal porcine hearts by radioimmunoassay disclosed abundant proBNP in the atria, whereas proBNP was undetectable in the ventricles. Laser confocal microscopy revealed proBNP in secretory granules of atrial but not in the ventricular myocardium of normal pigs. Mild streptozotocin-induced diabetes doubled the expression of BNP mRNA in porcine atrial myocardium (P =0.03), but was without effect on BNP mRNA in the ventricular myocardium. The data suggest that BNP mRNA processing and proBNP storage differ between the atrial and ventricular myocardium. The results also imply that diabetes increases cardiac BNP expression in a chamber-dependent manner.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"68 1","pages":"54-60"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83795487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 60