血栓抽吸治疗急性ST段抬高型心肌梗死前后神经内分泌因子水平的变化

目的探讨应用血栓抽吸装置GuardWire Plus^TM行血栓抽吸治疗急性sT段抬高型心肌梗死（STEMI）对神经内分泌因子水平、外周血肌钙蛋白（cTnI）、TIMI血流变化的影响及其临床价值。方法将2004年9月至2006年9月在我院行急诊PCI的72例STEMI患者分为两组，抽吸组（TA组，38例）血栓抽吸后支架置入；非抽吸组（NTA组，34例）单纯PCI。于手术当天、术后第1、2、3、5天分别测定外周血中内皮素（ET）、血浆肾素活性（PRA）、醛固酮（ALD）、血管紧张素Ⅱ（AngⅡ）、去甲肾上腺素（NE）、肾上腺素（E）的水平。于术前、术后4h、8h、12h、16h、24h、2d、3d、5d分别测定外周血中cTnI的水平。支架置入后常规行冠状动脉造影，观察心肌血流灌注情况，测定支架置入后两组患者的TIMI血流。比较术后2h心电图ST段回落。术后1周及3个月应用彩色超声心动图测定左室射血分数（LVEF），评价心功能。结果两组病例均成功置入支架，术前两组患者的神经内分泌因子水平均显著升高，两组间差异无统计学意义。浓度-时间曲线显示术后神经内分泌因子水平均迅速下降，TA组较NTA组ET、PRA、AngⅡ、ALD、NE、E等神经内分泌因子水平于术后第1天或第2天下降明显[ET：术前152．37ng／L比153．63ng／L（P：0．858），术后第1天128．11ng／L比147．07ng／L（P=0．037），术后第2天122．22ng／L比139．64ng／L（P=0．040）；PRA：术前2．87μL／（L·h）比2．87μL／（L·h）（P=0．998），术后第1天1．74μL／（L·h）比2．54μL／（L·h）（P=0．036），术后第2天1．70μL／（L·h）比2．29μL／（L·h）（P=0．032）；ALD：术前200．14pmol／L比181．19pmol／L（P=0．508），术第1天156．06pmol／L比172．19pmol／L（P=0．001）；AngⅡ：术前199．11ng／L比。212．32ng／L（P=0．539），术后第1天149．26ng／L比188．37ng／L（P=0．040），术后第2天135．57     

Systolic hypertension in the elderly: addressing an unmet need

Systolic hypertension is a major public health issue in the elderly and is often under-recognized and under-treated. The concept that systolic blood pressure increases with age should be considered a pathophysiologic concept. Aging of the cardiovascular system is accompanied by endothelial dysfunction, activation of the renin-angiotensin system and, consequently, vascular remodeling. This process leads to an increase in large artery stiffness and an increase in arterial wave reflections to the heart. These processes in daily clinical practice translate to an increase in systolic blood pressure, which is associated with increased cardiovascular morbidity and mortality. Evidence-based medicine recommendations to treat systolic hypertension in the elderly are based on landmark and recent clinical trials, which clearly demonstrated that treatment of isolated systolic hypertension is associated with significant decreases in cardiovascular morbidity and mortality. However, treatment of systolic hypertension in older adults remains disappointing because therapeutic goals often are not reached. Therefore, emphasis should be placed on the treatment of systolic hypertension in the elderly, and there is need for more effective, individualized antihypertensive therapy.     

心房颤动患者循环血浆肾素、血管紧张素Ⅱ和醛固酮的变化及临床意义

目的 分析心房颤动患者循环血浆肾素、血管紧张素Ⅱ(AngⅡ)、醛固酮(Ald)的水平变化,并探讨其临床意义。方法入选42例患者,男19例,女23例,年龄37-80(63.02±10.66)岁。按有无心房颤动病史分为三组:窦性心律组(SR组)14例,阵发性心房颤动组(pAF组)15例,慢性心房颤动组(cAF组)13例。应用放射免疫方法测定循环血浆肾素、AngⅡ、Ald浓度。结果cAF组患者平均左心房直径与SR组和pAF、组相比明显增大(分别增大45.3％和31.8％,P<.01),而且cAF组患者循环血浆肾素、AngⅡ、Ald浓度与SR组相比明显升高(分别升高83.3％、61.7％、34.2％,P<0.01-0.02)。三组患者左心房直径与其循环血浆肾素、AngⅡ、Ald浓度变化具有明显的正相关关系(P<0.05-0.01)。结论心房颤动时存在肾素-血管紧张素系统(RAS)和Ald的激活。RAS和Ald可能参与了心房结构重构的发生。Ald的作用靶点可能主要是心房间质。     

A Nonpeptide,Piperidine Renin Inhibitor Provides Renal and Cardiac Protection in Double-Transgenic Mice Expressing Human Renin and Angiotensinogen Genes

Introduction  Controlling hypertension by angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), mechanisms that inhibit later pathway steps in the renin–angiotensin system (RAS), have clinically afforded protection against cardiac and renal disease. Materials and methods  In order to determine if blocking the RAS rate-limiting step of angiotensin II generation via renin inhibition could afford similar end organ protection in a human-relevant preclinical model, this study investigated the cardiac and renal effects of a nonpeptide, piperidine renin inhibitor (RI; 100 mg/kg/day PO) in double transgenic mice (dTGM) which express both human renin and angiotensinogen genes. RI was compared to the ARB, candesartan (3 mg/kg/day PO), and to the ACEI, enalapril (60 mg/kg/day PO) in a 4-week dosing paradigm. These doses of RI, ACEI and ARB were previously found to normalize mean blood pressure (MBP) to 110 + 3, 109 + 7 and 107 + 6 mmHg, respectively, after 1 day of treatment. Results and discussion  In the dTGM, PRA, plasma aldosterone, GFR, microalbuminuria and left ventricular free wall thickness (LVH) were higher than in the wild type C57BL/6 mice. Microalbuminuria and LVH were significantly reduced by 93% and 9% for the RI, 83% and 13% for enalapril and 73% and 6% for candesartan, respectively. PRA and aldosterone were reduced by the RI 56% and 23%, respectively. These results suggest that the RI provides protection against cardiac and renal disease, similar to ARB and ACEI.     

The role of prostaglandins in the alpha- and beta-adrenoceptor mediated renin release response to graded renal nerve stimulation

The role of prostaglandins in the renin release response to renal nerve stimulation (RNS) at different intensities was examined in the anaesthetized dog. The animals were divided into two groups receiving either low or high level RNS, defined by the frequencies of stimulation producing reduction in renal blood flow by 5% or less and 50%. Indomethacin or diclofenac sodium (5 mg/kg i.v.), prostaglandin synthesis inhibitors, did not affect the renin release response to high level RNS by 31±8% (P<0.01). Addition of metoprolol, (0.5 mg/kg i.v.) beta-1-adrenoceptor antagonist, to indomethacin or diclofenac sodium resulted in a greater reduction (68±6%P<0.01) of the renin release response to high level RNS compared to that produced by either drug alone. Metoprolol, alone, reduced the renin release response to high level RNS by 37±14% (P<0.05). Phenoxybenzamine (0.6 g·kg^–1·min^–1), alphaadrenoceptor antagonist, into the renal artery practically abolished the renal vasoconstrictor response to high level RNS and reduced the renin release response by 50±7% (P<0.01). Addition of metoprolol to phenoxybenzamine practically abolished the renal vasoconstrictor response and the renin release response to high level RNS; 94±4% (P<0.01). Addition of phenoxybenzamine to indomethacin or diclofenac sodium practically abolished the renal vasoconstrictor response to high level RNS but did not produce any greater reduction of the renin release response than that produced by either drug alone. These findings suggest that low level RNS results in renin release which is not dependent on prostaglandins. High level RNS results in renin release which is partly mediated by beta-1-adrenoceptors and partly related to alpha-adrenoceptor mediated renal vasoconstriction. Prostaglandins are not involved in the beta-adrenoceptor mediated renin release but are involved in the renin release deriving from alpha-adrenoceptor mediated renal vasoconstriction.     

血浆醛固酮与肾素活性比值测定方法标准化问题的探讨

血浆醛同酮与血浆肾素活性比值(ARR)已广泛应用在高血压患者中筛查原发性醛同酮增多症(原醛).研究表明,不同的临床状况(测定方法)会得出不同的ARR.由于没有统一的ARR标准,使得其临床应用难以适从.因此,应该根据所选用的测定方法和本单位的试验条件,采用相应的,同时具最高敏感性、特异件和准确件的ARR.近年来通过控制测定条件,即所谓测定方法标准化,包括:停用降压药2～4周、取同定体位、上午8:00～12:00之间采血、充分钠摄入以及低血钾者补钾等,发现原醛的ARR范围大致在23.6～26.0 ng·dl-1·ng-1·ml-1·h-1之间,说明ARR筛查方法标准化有助于确定和统一筛查原醛的ARR标准.     

p90 ribosomal S6 kinase regulates activity of the renin-angiotensin system: a pathogenic mechanism for ischemia-reperfusion injury

Increasing evidence suggests that local renin-angiotensin system (RAS) plays an important role in cardiac diseases. Elevated p90 ribosomal S6 kinase (RSK) activity has been observed in diabetic animal, as well as in human failing hearts. We hypothesize that RSK mediates cardiac dysfunction by up regulating local RAS signaling. In the present study, we show that the prorenin mRNA level was significantly increased (~ 5.6-fold) in transgenic mouse hearts with cardiac specific expression of RSK (RSK-Tg). The RSK-Tg mice were more vulnerable to ischemia/reperfusion (I/R) injury than non-transgenic littermate controls (NLC). To further understand the direct contribution of cardiac renin to I/R injury, we used a Langendorff system to evaluate the effect of renin inhibition by aliskiren in RSK-Tg mouse hearts. In the vehicle-perfused group, I/R significantly decreased left ventricular developed pressure (LVDP) in RSK-Tg hearts compared to NLC (7% versus 60% of the baseline). However, aliskiren perfusion significantly increased LVDP in RSK-Tg (7% to 61%, p < 0.01) but not in NLC hearts (60% to 62%, n.s.). The protective effect of aliskiren in RSK-Tg hearts was further demonstrated with positive (contraction) dp/dt (6.5% to 63%, p < 0.01) and rate pressure product (RPP) (5% to 51%, p < 0.01). Moreover, aliskiren significantly decreased I/R induced infarction in RSK-Tg (60% to 32%, p < 0.01), compared to NLC hearts (37% to 32%, n.s.). These results suggest that RSK plays a crucial role in regulating local cardiac renin, which contributes to I/R induced cardiac injury and dysfunction. Thus, renin inhibition may provide an alternative therapeutic strategy under conditions of increased RAS.     

培哚普利对肾性高血压大鼠肾脏血管紧张素转换酶2的影响

目的采用两肾一夹(2K1C)高血压大鼠模型,了解培哚普利对高血压大鼠肾脏血管紧张素转换酶2(ACE2)表达的影响。方法40只雄性大鼠随机分为5组:正常对照组;2K1C高血压组;缬沙坦组;高剂量培哚普利组;低剂量培哚普利组。给药8周后,计算心重指数,放射免疫分析法测定血浆血管紧张素(Ang)Ⅱ水平,逆转录聚合酶链反应(RT-PCR)检测肾脏ACE2 mRNA表达,免疫组织化学法检测肾脏ACE2表达。结果培哚普利和缬沙坦治疗都明显降低高血压大鼠血压(P<0.01);RT-PCR和免疫组织化学染色结果显示2K1C高血压大鼠肾脏ACE2表达较正常大鼠降低(P<0.05);经培哚普利及缬沙坦治疗后大鼠ACE2表达明显高于2K1C高血压组(P<0.05)。高剂量培哚普利组血浆AngⅡ降低较缬沙坦组明显(P<0.01)。2K1C高血压大鼠心重指数明显高于各给药组(P<0.01)。结论2K1C高血压大鼠肾脏组织中ACE2表达降低,培哚普利及缬沙坦在降压的同时能增加肾脏组织ACE2的表达。     

肾素血管紧张素系统基因多态性与高血压及血管紧张素转换酶抑制剂的降压疗效的关系

高血压病是一种环境与遗传因素相互作用的疾病 ,它是冠心病、脑卒中、左心室肥厚、急性心肌梗死等心血管疾病的独立危险因素 ,寻找其相关及致病基因为近年研究的热点 ,特别是肾素血管紧张素系统基因的多态性与高血压的相互关系成为分子生物学研究的热点。这些研究表明高血压可能是基因与基因、基因与环境共同作用的结果。在高血压的治疗中个体对血管紧张素转换酶抑制剂类药物降压疗效的反应存在着差异 ,遗传因素决定了部分差异。     

Endogenous urocortins reduce vascular tone and renin-aldosterone/endothelin activity in experimental heart failure.

AIMS: To investigate the role of the endogenous urocortin peptides in heart failure (HF) through blockade of the corticotropin-releasing factor receptor 2 (CRF-R2). METHODS AND RESULTS: Eight sheep were administered the CRF-R2 antagonist CRF(9-41) (1.5 mg bolus) before (Normal) and after development of pacing-induced HF. Compared with controls, CRF(9-41) in HF significantly increased mean arterial pressure (MAP) (71+/-2 vs. 75+/-2 mmHg, P=0.0024) and calculated total peripheral resistance (CTPR) (33.3+/-5.2 vs. 39.4+/-5.9 mmHg/L/min, P=0.0455). Similar trends were observed in the Normal state (MAP 87+/-1 vs. 89+/-2 mmHg, P=0.0689; CTPR 21.9+/-2.0 vs. 24.4+/-2.4 mmHg/L/min, P=0.0731). Left atrial pressure was elevated similarly in both states (Normal P=0.0013; HF P=0.0298), whereas cardiac output tended to be reduced (Normal P=0.0614). CRF(9-41) increased plasma urocortin-I (Normal 10.3+/-0.8 vs. 19.8+/-1.3 pmol/L, P<0.001; HF 14.4+/-0.9 vs. 25.3+/-0.8 pmol/L, P<0.001), renin (Normal 0.34+/-0.06 vs. 0.41+/-0.02 nmol/L/hr, P=0.013; HF 1.14+/-0.29 vs. 1.57+/-0.36 nmol/L/hr, P=0.0326), aldosterone (Normal 370+/-62 vs. 563+/-99 pmol/L, P=0.0813; HF 662+/-141 vs. 1024+/-209 pmol/L, P=0.095), and endothelin-1 (HF 3.18+/-0.18 vs. 4.74+/-1.04 pmol/L, P=0.0087). MAP, CTPR, renin, and endothelin-1 responses to CRF-R2 antagonism were significantly greater in HF than in the Normal state (P=0.049, 0.0427, 0.0311, and 0.0412, respectively). CONCLUSION: These data suggest that the endogenous urocortin peptides contribute to the suppression of vascular tone and renin-angiotensin-aldosterone/endothelin activation in HF and thus, play a protective compensatory role in this disorder.