Sex differences in the developmental programming of hypertension

Experimental models of developmental programming provide proof of concept and support Barker's original findings that link birthweight and blood pressure. Many experimental models of developmental insult demonstrate a sex difference with male offspring exhibiting a higher blood pressure in young adulthood relative to their age‐matched female counterparts. It is well recognized that men exhibit a higher blood pressure relative to age‐matched women prior to menopause. Yet, whether this sex difference is noted in individuals born with low birthweight is not clear. Sex differences in the developmental programming of blood pressure may originate from innate sex‐specific differences in expression of the renin angiotensin system that occur in response to adverse influences during early life. Sex differences in the developmental programming of blood pressure may also involve the influence of the hormonal milieu on regulatory systems key to the long‐term control of blood pressure such as the renin angiotensin system in adulthood. In addition, the sex difference in blood pressure in offspring exposed to a developmental insult may involve innate sex differences in oxidative status or the endothelin system or may be influenced by age‐dependent changes in the developmental programming of cardiovascular risk factors such as adiposity. Therefore, this review will highlight findings from different experimental models to provide the current state of knowledge related to the mechanisms that contribute to the aetiology of sex differences in the developmental programming of blood pressure and hypertension.     

持续小剂量西地那非对良性前列腺增生患者组织内皮素-1及其受体的影响

目的 观察持续口服小剂量西地那非对良性前列腺增生(BPH)患者前列腺组织中内皮素-1(ET-1)及其受体A、B ETAR/ETBR基因表达的影响.方法 32例BPH患者随机归入治疗组及对照组,每组各16例.治疗组每日口服西地那非25 mg,为期12周.对照组未服用药物.应用免疫组化、酶联免疫吸附法及RT-PCR方法检测并比较两组前列腺组织FT-1及其ETAR的表达.结果 ET-1、ETAR mRNA及ETBR mRNA在前列腺组织中的表达治疗组明显低于对照组[(53.31±18.56)ng/kg比(83.34±31.38) ng/kg、0.356±0.056比0.624±0.083、0.721±0.083比0.933±0.905,t=-3.295、10.715、6.937,均P＜0.001].结论 持续口服小剂量西地那非能降低BPH组织中ET-1及其受体ETA/B基因的表达量.     

Endothelin-1 derived from spleen-activated Rho-kinase pathway in rats with secondary biliary cirrhosis

Aim: Splenectomy or partial splenic embolism has been reported to improve liver function in patients with hypersplenism and liver dysfunction. The aim of this study was to investigate the mechanism of improvement after splenectomy. Methods: Liver cirrhosis was induced by bile duct ligation (BDL). Rats underwent sham operation, splenectomy (Sp group), BDL, or BDL plus splenectomy (BDL + Sp group), and were subjected to experiments at 2 weeks after the operation. Portal venous pressure (PVP) and hepatic tissue blood flow (HTBF) were measured in each group. The plasma concentration of endothelin‐1 (ET‐1) and endothelial nitric oxide synthase (eNOS), RhoA and Rho‐kinase expressions were studied. Results: There were significant differences in PVP (17.9 ± 0.91 vs 23.3 ± 3.91 cmH₂O; P < 0.01) and HTBF (16.6 ± 1.72 vs 13.3 ± 1.82 mL/min; P < 0.01) between the BDL + Sp and BDL groups. In the liver of BDL rats, eNOS phosphorylation and NOx levels were decreased, accompanied by RhoA activation compared with the BDL + Sp group. Splenectomy decreased serum ET‐1 levels, RhoA activation and consequently increased eNOS phosphorylation. Conclusion: ET‐1 derived from the spleen might increase intrahepatic resistance by downregulating Rho signaling in liver cirrhosis. Splenectomy for splenomegaly in liver cirrhosis might partially improve liver function by enhancing intrahepatic microcirculation.     

内皮素A受体拮抗剂BQ_（123）抗内皮素的心律失常作用

雄性ＳＤ大鼠４２只经冠状动脉口注射内皮素Ａ（ＥＴ＿Ａ）受体拮抗剂ＢＱ＿（１２３），观察其对内皮素致心律失常作用的影响。结果表明，ＢＱ＿（１２３）０．１１～１．７５μｇ／ｋｇ预处理后，内皮素引起的心律失常记分（ＡＳ）呈剂量依赖性降低趋势，ＢＱ＿（１２３）为７μｇ／ｋｇＡＳ降为０，与内皮素（ＥＴ）组比较有非常显著差异。ＢＱ＿（１２３）拮抗内皮素致心律失常作用可能通过拮抗ＥＴ＿Ａ受体实现。     

双胸蚯蚓溶栓酶对沙土鼠脑缺血再灌注脑匀浆中ET,TXB_2和6-keto-PGF_1α的影响

应用放免分析技术测定沙土鼠脑缺血再灌注模型脑匀浆中ET,TXB_2和6-keto-PGF_(1α)含量,并用干湿重量法测定脑组织含水量。结果显示双胸蚯蚓溶栓酶能明显降低沙土鼠脑缺血再灌注脑匀浆中ET和TXB_2的含量,减少脑组织含水量。提示双胸蚯蚓溶栓酶对缺血性脑损伤起保护作用。     

老年高血压患者脉压与动脉内皮功能损害的关系

目的 探讨老年高血压患者脉压与动脉内皮功能损害的相关性。方法 对160例原发性高血压患者按脉压分成四组,同时测定每个组的血浆内皮素-1（ET-1）和一氧化氮（NO）的水平情况。结果 老年高血压患者脉压与ET-1呈显著性正相关（r=-0．185,P〈0．01）,与NO呈显著性负相关（r=-0．162,P〈0．05）,与ET-1和NO的比值呈显著性正相关（r=0．212,P〈0．01）。结论 高血压患者脉压与动脉内皮功能损害关系密切,可作为评估和预测高血压患者动脉内皮功能损害的指标。     

INTRACELLULAR REDISTRIBUTION OF CARDIAC ENDOTHELIN- 1 RECEPTOR IN RAT DURING MYOCARDIAL HYPERTROPHY

INTRODUCTION Pressure overload is the most common causative factor on myocardial hypertrophy in vivo. However, it is still unclear about the mechanism that the signal of pressure overload is transmitted to cardiac myocytes. Recent studies have demonstrated that endothelin (ET) has hormone- like or growth factor- like properties in a wide variety of mammalian cells, including cardiac myocytes. Several lines of evidences based on cardiac expression of prepro ET- 1 gene (1－ 3) suggest the …     

拉西地平对高血压疗效及血管活性物质的影响

用拉西地平治疗原发性高血压(EH)患者40例,服拉西地平1次/d,4～6mg/次,治疗4周,降低血压的显效率67.5％,总有效率92.5％,其中Ⅰ期、Ⅱ期的总有效率(100％和96.5％)明显高于Ⅲ期(33.3％),平均收缩压(SBP)、舒张压(DBP)和平均动脉压(MAP)分别下降3.77(28.40)、2.62(19.73)和3.02(22.64)kPa(mmHg),24h动态血压监测(n=20)证实拉西地平可降低白天及夜间的平均SBP、DBP和MAP(p<0.01),同时降低血浆内皮素、血管紧张素Ⅱ水平。提示拉西地平降压稳定、持久、剂量小,每日只服1次,耐受性良好。