慢性缺氧对肺动脉内皮依赖性和非内皮依赖性舒张反应的影响

本实验用生物测定法观察了模拟海拔5000m高度连续缺氧20d对大鼠肺动脉内皮依赖性和非内皮依赖性舒张反应的影响。结果显示慢性缺氧明显抑制了肺内和肺外动脉对乙酰胆碱、ATP、硝普钠和异丙肾上腺素舒张反应的敏感性和反应性。在浓度为10~(-6)mol/L时,缺氧组大鼠肺内动脉对乙酰胆碱、硝普钠和异丙肾上腺素的舒张反应分别只有对照组大鼠的61.3％、75.9％和61.7％,对浓度为1.8×10~(-5)mol/L的ATP的舒张反应只有对照组大鼠的64.9％。研究表明,ATP和乙酰胆碱主要是通过内皮舒张因子使肺动脉产生内皮依赖性舒张反应,硝普钠和异丙肾上腺素分别通过直接激活血管平滑肌细胞鸟苷酸环化酶和β受体使血管产生非内皮依赖性舒张反应。缺氧同时抑制了肺动脉内皮依赖性和非内皮依赖性舒张反应,提示慢性缺氧可能抑制了正常肺内舒血管活性物质的生理作用。     

川芎嗪对缺氧大鼠和雪貂肺血管的舒张作用

用大鼠在体肺灌流和雪貂左下肺叶活体灌流方法比较了川芎嗪对缺氧、血管紧张素Ⅱ、高钾、almitrine等所致肺血管收缩的舒张效应。实验结果表明,川芎嗪能使缺氧引起的收缩肺血管明显舒张,此效应可能不通过血管紧张素系统。对高钾引起的肺血管收缩,川芎嗪的抑制作用明显小于异搏定。川芎嗪对肺血管的舒张效应表明缺氧和almitrine对肺血管的作用相近。在急性缺氧情况下,川芎嗪对肺血管的舒张作用比对体血管强,这一点对缺氧性肺动脉高压的防治是很有用的。     

慢性缺氧对大鼠肺动脉内皮依赖性舒张反应及cGMP含量的影响

本实验观察了慢性缺氧对大鼠肺动脉内皮依赖性舒张反应和肺动脉内环磷酸鸟苷(cGMP)含量的影响。乙酰胆碱(ACh)和三磷酸腺苷(ATP)可使正常大鼠的离体肺动脉产生内皮依赖性舒张反应,其舒张作用不受消炎痛的影响,但被甲烯蓝完全抑制。慢性缺氧明显减低了 ACh 和 ATP 诱发的大鼠肺内和肺外动脉的内皮依赖性舒张反应。当 ACh 浓度为10~(-6)mol/L 时,缺氧组大鼠肺内和肺外动脉舒张百分数分别为对照组的61.3%和59.2%;当 ATP浓度为1.8×10~(-5)mol/L 时,缺氧组大鼠肺内和肺外动脉舒张反应分別为对照组的64.9%和55.3%。慢性缺氧也减低了硝普钠(SNP)诱发的大鼠肺动脉非内皮依赖性舒张反应。慢性缺氧显著减低了大鼠肺动脉内 cGMP 的含量。缺氧组和对照组大鼠肺动脉内 cGMP 的基础含量分别是51.9±5.7 pmol/g wet wt.(n=14)和84.9±9.7 pmol/g wet wt.(n=14),p<0.01;经 10~(-7)mol/L ACh 刺激后分别是91.4±7.3 pmol/g wet wt.(n=5)和240.8±30.6pmol/g wet wt.(n=5),p<0.01。慢性缺氧可能抑制了肺动脉平滑肌细胞胞浆中可溶性鸟苷酸环化酶,从而减低了肺动脉对内皮舒张因子和 SNP 的舒张反应性。     

慢性缺氧对自发性高血压大鼠血液动力学和血管反应性的影响

本研究观察了鼠龄10周的自发性高血压大鼠(SHR)在慢性缺氧条件下(模拟海拔5000m,15d)体动脉压(SBP)、平均肺动脉压(MPAP)、左、右心室收缩指数(LVIC、RVIC)和舒张指数(LVIR、RVIR)以及血管反应性的变化。结果表明,慢性缺氧明显阻抑SHR大鼠SBP升高(P<0.05),但使SHR大鼠MPAP升高(P<0.001)。慢性缺氧还可增大SHR大鼠LVIC和LVIR,增强SHR大鼠胸主动脉对乙酰胆碱(ACh)的舒张反应,减弱其对5-羟色胺(5-HT)的收缩反应。SHR大鼠肺动脉对ACh和5-HT的反应则与主动脉相反。实验结果提示,慢性缺氧阻抑SHR大鼠血压升高与血管反应性的改变有关。     

Apelin对大鼠离体肺动脉环的舒张作用及与一氧化氮的关系

目的：探讨新的小分子活性肽Apelin对大鼠离体肺动脉环的舒张作用及与一氧化氮（NO）途径的关系,并比较低氧大鼠的肺动脉环对Apelin的舒张反应与正常大鼠的差异。方法：36只大鼠随机分为正常组与低氧组;采用离体血管环灌流法,检测Apelin对去甲肾上腺素（NE）预收缩的大鼠离体肺主动脉环的舒张效应,观察去内皮或用一氧化氮合酶抑制剂（L-NAME）、可溶性鸟苷酸环化酶（sGC）抑制剂（ODQ）孵育后该舒张率的变化。结果：①在正常组大鼠肺动脉环,Apelin（0.01~100 nmol/L）具有浓度依赖性的舒张效应。去除内皮后,Apelin对NE预先收缩的肺血管舒张效应明显减弱（P〈0.01）。L-NAME或ODQ预孵育后,Apelin的舒张效应均明显减弱（P均〈0.01）。②低氧组大鼠的肺动脉环对Apelin的舒张反应明显低于正常组大鼠,在最大浓度100 nmol/L时,Apelin的效应低60.45%（P〈0.01）,而两组EC50相比差异无显著性（P〉0.05）。结论：Apelin具有内皮依赖性的舒张肺动脉环的作用,该效应与NO-sGC-cGMP信号途径有关;低氧大鼠的离体肺动脉环对Apelin的舒张反应减弱。     

血管钠肽、 C型钠尿肽和心房钠尿肽舒血管作用的对比

本实验采用离体血管灌流方法,观察和比较血管钠肽（ＶＮＰ）,Ｃ型钠尿肽（ＣＮＰ）和心房钠尿肽（ＡＮＰ）对大鼠肺动脉,腹主动脉和腹腔静脉的舒张作用。．结果表明,ＶＮＰ,ＣＮＰ和ＡＮＰ对离体大鼠的保留内皮与去内皮的肺动脉,腹主动脉和腹腔静脉均有浓度依赖性舒张作用。     

血管内皮细胞在氧自由基所致肺内动脉收缩反应中的作用

应用生物测定法观察黄嘌呤(X)-黄嘌呤氧化酶(XO)系统产生的氧自由基对正常、缺氧(5000m,10d)Wistar大鼠肺内动脉环张力的影响及内皮细胞在其中的作用。发现XO在一定浓度范围内产生的氧自由基可引起肺内动脉剂量依赖性收缩。正常鼠肺内动脉去内皮或加内皮舒张因子 (EDRF) 灭活剂后,此剂量依赖性收缩明显增强。慢性缺氧大鼠肺内动脉无论内皮完整与否,上述收缩反应均增强。提示缺氧使内皮细胞和(或)EDRF的功能受到损害。应用超氧化物歧化酶(铜锌SOD),在正常或缺氧鼠肺内动脉上可分别加强或恢复内皮细胞抑制氧自由基的缩血管作用。提示慢性缺氧时,内皮细胞和(或)EDRF受到超氧阴离子的严重破坏,这一机制可能在缺氧性肺动脉高压的形成中起重要作用。     

肺纤维化初期肺动脉高压大鼠肺动脉反应性的变化

目的：观察肺纤维化初期肺动脉高压大鼠肺动脉血管反应性的变化。方法：66只雄性SD大鼠,随机分为博莱霉素（BLM）组和手术对照（Sham）组。BLM组为气管内一次性滴注BLM（5 mg/kg）;Sham组为气管内滴注等容量的生理盐水（NS）。应用离体血管张力检测技术测定大鼠肺动脉血管反应性变化;用HE显示肺动脉壁病理形态学变化;Masson染色检测肺纤维化程度;右心漂浮导管技术测定大鼠平均肺动脉压。结果：①BLM组大鼠的肺动脉血管（保留内皮和去内皮）对苯肾上腺素（PE）的收缩反应均弱于Sham组（P均〈0.05）。②BLM组大鼠肺动脉血管（保留内皮）对氯化乙酰胆碱（Ach）的舒张反应明显弱于Sham组（P〈0.01）。③Sham组有内皮的肺动脉血管对L-NAME和PE联合作用的收缩反应明显强于PE单独作用（P〈0.01）,而BLM组有内皮肺动脉血管对L-NAME和PE联合作用的收缩反应与对PE单独作用比,其差异无统计学意义（P〉0.05）。④BLM组肺动脉内皮细胞脱落。⑤BLM组大鼠肺组织呈现纤维增生初期的病理特征,且大鼠的平均肺动脉压明显高于Sham组（P〈0.05）。结论：肺纤维化形成初期肺动脉高压大鼠肺动脉血管反应性出现异常。     

血管内皮舒张因子在氧自由基所致慢性缺氧大鼠肺内动脉收缩中的作用

以黄嘌岭(X)-黄嘌呤氧化酶(XO)系统产生氧自由基,应用微量生物测定法观察慢性缺氧(5000m,10d)对大鼠氧自由基所致肺内动脉收缩的影响及内皮舒张因子(EDRF)在其中的作用。慢性缺氧大鼠有内皮的肺内动脉环对氧自由基的收缩反应较正常环境中的对照动物明显增强,加入EDRF灭活剂还原型血红蛋白(RHb)后更加显著;而加入超氧化物歧化酶(铜锌SOD)后则减弱,甚至消除。反之,不论加入RHb或SOD对氧自由基所致去内皮肺内动脉环的收缩反应均无明显影响。上述结果表明慢性缺氧引起肺内动脉收缩增强与EDRF有密切关系:慢性缺氧可能使EDRF的作用减弱,肺内动脉对氧自由基的反应性增强。表示EDRF及其与氧自由基的关系在慢性缺氧性肺动脉高压的形成中可能具有十分重要的意义。     

心房钠尿肽对内毒素血症大鼠肺动脉和主动脉舒缩的影响

目的:探讨心房钠尿肽(ANP)对内毒素血症大鼠(ETR)肺动脉和主动脉内皮和平滑肌细胞的调节作用.方法:24只雄性SD大鼠随机分为对照组,模型组(LPS组),治疗组(ANP组).各组分别静脉注射生理盐水、2 mg/kg的LPS和2 mg/kg LPS与2μg/kg的ANP,4 h后处死动物分离肺动脉、主动脉,进行离体血管务体外灌注实验.结果:LPS组、ANP治疗组主动脉环和LPS组肺动脉环对去甲肾上腺素(NE)引起的收缩作用在NE低浓度时较对照组减弱(P＜0.01),在较高浓度时较对照组均明显增强(P＜0.01);主动脉环ANP治疗组与LPS组无显著差异(P＞0.05);肺动脉环ANP治疗组与对照组相比无显著差异(P＞0.05).ANP可明显改善ETR离体主动脉和肺动脉对乙酰胆碱(ACh)的舒张反应(P＜0.01),ANP可提高ETR离体主动脉和主动脉环对硝普钠(SNP)引起的舒张反应的敏感性(P＜0.01).结论:ANP对ETR肺动脉和主动脉内皮和平滑肌细胞可能存在调节作用.     

The cardioprotective effect of isosteviol on rats with heart ischemia-reperfusion injury

This study was designed to assess the cardioprotective effect of isosteviol on rats with heart ischemia-reperfusion (IR) injury and to explore the mechanism of action of the compound. Sprague Dawley rats were divided into 8 groups (n=10-12): a sham-operated control and 7 ischemia-reperfusion groups (IR control, 3 isosteviol pre-treated (0.5, 1.0 and 2.0 mg kg(-1)), ligustrazine pre-treated, 5-hydroxydecanoate (5-HD) pre-treated and 5-HD+ isosteviol pre-treated groups). IR was produced by occluding the left coronary artery for 30 min followed by re-opening the artery for 90 min. The compounds under investigation were administered intravenously 10 min prior to occluding the artery. Hemodynamic parameters (+/-dp/dt(max), LVSP, LVDevP, MAP), heart rate, ventricular tachycardia (VT) and ventricular fibrillation (VF) were determined during the IR period. The myocardial infarct size, activities of serum lactate dehydrogenase and creatine kinase were determined at the end of the experiment. In the isosteviol pre-treated groups, the hemodynamic parameters were improved and the myocardial infarct size, the activities of serum enzymes, and the incidences of VT and VF were all decreased when compared to the control group. These effects of isosteviol were similar to that of a traditional cardioprotective agent, ligustrazine. The 5-HD+ isosteviol group displayed parameters that were between those in the equivalent isosteviol pre-treated group and the IR control group. In conclusion, damage due to a standard rat heart IR injury was reduced by pretreatment with intravenous isosteviol, and this effect was partly attenuated by a mitochondrial ATP-sensitive potassium channel blocker, 5-HD.     

Differential effects of prostaglandins A1 and A2 on pulmonary vascular resistance in the dog.

The effects of PGA1 and PGA2 were studied in the canine pulmonary vascular bed. Infusion of PGA1 into the lobar artery decreased lobar arterial and venous pressure but did not change left atrial pressure. In contrast, PGA2 infusion increased lobar arterial and venous pressure and the effects of this substance were similar in experiments in which the lung was perfused with dextran or with blood. These data indicate that under conditions of controlled blood flow PGA1 decreases pulmonary vascular resistance by dilating intrapulmonary veins and to a lesser extent vessels upstream to the small veins, presumably small arteries. The present data show that PGA2 increases pulmonary vascular resistance by constricting intrapulmonary veins and upstream vessels. The predominant effect of PGA2 was on upstream vessels and the pressor effect was not due to interaction with formed elements in the blood or platelet aggregation.     

Inactivation of G(i) proteins by pertussis toxin diminishes the effectiveness of adrenergic stimuli in conduit arteries from spontaneously hypertensive rats

Treatment with pertussis toxin (PTX) which eliminates the activity of G(i) proteins effectively reduces blood pressure (BP) and vascular resistance in spontaneously hypertensive rats (SHR). In this study we have compared the functional characteristics of isolated arteries from SHR with and without PTX-treatment (10 microg/kg i.v., 48 h before the experiment). Rings of thoracic aorta, superior mesenteric artery and main pulmonary artery were studied under isometric conditions to measure the reactivity of these vessels to receptor agonists and to transmural electrical stimuli. We have found that the treatment of SHR with PTX had no effect on endothelium-dependent relaxation of thoracic aorta induced by acetylcholine. In PTX-treated SHR, the maximum contraction of mesenteric artery to exogenous noradrenaline was reduced and the dose-response curve to cumulative concentration of noradrenaline was shifted to the right. Similarly, a reduction in the magnitude of neurogenic contractions elicited by electrical stimulation of perivascular nerves was observed in the mesenteric artery from PTX-treated SHR. PTX treatment of SHR also abolished the potentiating effect of angiotensin II on neurogenic contractions of the main pulmonary artery. These results indicate that PTX treatment markedly diminishes the effectiveness of adrenergic stimuli in vasculature of SHR. This could importantly affect BP regulation in genetic hypertension.     

Distribution of the vasoconstrictor and vasorelaxant effects of norbormide along the vascular tree of the rat

Norbormide is a vasoconstrictor of rat peripheral arteries and a relaxant in rat aorta. To characterise norbormide actions within the rat vascular tree we have investigated its effects on the contractile function of rings from several arteries and veins. A maximal norbormide concentration (50 microM) failed to contract thoracic aorta and carotid artery, whereas in pulmonary artery, abdominal aorta, iliac, caudal, and femoral arteries it induced a contractile effect that was respectively 4.8 +/- 0.6, 18.4 +/- 1.5, 39 +/- 5, 144 +/- 7, and 260 +/- 22% of that induced by 90 mM KCl. In pulmonary, carotid, and iliac arteries, and in thoracic and abdominal aorta, 50 microM norbormide inhibited KCl-induced responses. Norbormide (50 microM) contracted all veins investigated. The effect, expressed as % of KCl-induced contraction, was 121 +/- 25, 154 +/- 14.5, 154 +/- 18.2, 203 +/- 19, and 267 +/- 33 for pulmonary vein, thoracic and abdominal vena cava, iliac and jugular veins, respectively. In jugular vein, as previously shown in rat caudal artery, norbormide contraction was abolished in Ca2+-free medium, was unaffected by the Ca2+ channel blocker nifedipine, and was relaxed by SK&F 96365, a blocker of store-operated Ca2+ channels. In conclusion: i) rat veins represent the main target for contractile norbormide action; ii) in both artery and veins norbormide contractions are generally inversely related to the calibre of the vessel; iii) norbormide-induced contraction is mediated by the same mechanism/s in arteries and veins; iiii) in norbormide-contracted arteries the drug activates both contractile and relaxing mechanisms.     

Enhanced photorelaxation in aorta, pulmonary artery and corpus cavernosum produced by BAY K 8644 or N-nitro-L-arginine.

Segments of endothelium-denuded aorta, pulmonary arterial rings and strips of corpus cavernosum from rabbits were superfused with Krebs medium. Photorelaxation elicited by ultraviolet light (366 nm) was significantly enhanced by either BAY K 8644 (20 nM) or N-nitro-L-arginine (100 and 500 microM) and was associated with increased cyclic GMP. This action of both drugs was greater in pulmonary artery than aorta and corpus cavernosum and persisted in vascular rings for 90 min after drug removal. The effect was significantly attenuated by hemoglobin (10 microM) but was unaltered by superoxide dismutase (30 u/ml). The mechanism of such photosensitization is presently unclear.     

Cooling is a potent vasodilator of deep vessels in the rat.

The objectives of this study were to determine the effect of cooling on smooth muscle tone of the pulmonary artery and aorta and to clarify the basic mechanism of these responses. We recorded isometric tension in smooth muscle strips of rat pulmonary artery and aorta in organ baths during stepwise cooling. Cooling responses were tested before and after the addition of various standard agents that interfere with known neurogenic (autonomic blockers, tetrodotoxin) and myogenic mechanisms (calcium channel blockers) of relaxation. We also examined the hypothesis of the presence of a cooling-released substance. Stepwise cooling (37degrees C to 4 degrees C) of aortic smooth muscle induced reproducible graded relaxations that were inversely proportional to temperature. Cooling-induced relaxation was not dependent on a neural mechanism nor the release of neurotransmitters or a cooling-released substance such as NO or CO. Cooling of pulmonary arterial and aortic smooth muscle preparations induced a graded myogenic relaxation inversely proportional to the cooling temperature. The mechanism is not dependent on local nervous or known mediators but related to a direct physico-chemical effect of cooling.     

Calmodulin inhibitors suppress calcium signaling from serotonin receptors in smooth muscle cells and abolish vasoconstrictive response on intravenous introduction of serotonin

Comparative study of the effect of calmodulin inhibitors trifluoperazine, W-12, and W-13 and the TRPV1 channel blocker capsazepine on receptor-dependent calcium metabolism in smooth muscle cells of the rat aorta and on the contraction of the isolated rat aorta was performed. Trifluoperazine almost completely abolishes an increase in free cytoplasmic calcium concentration in smooth muscle cells isolated from the rat aorta and smooth muscle cells of the A7r5 line in response to serotonin and does not affect cellular reaction to vasopressin and angiotensin II. W-12 and W-13 also do not attenuate responses to vasopressin and angiotensin II and reduces by two times free cytoplasmic calcium concentration elevation in response to serotonin. The efficiency of calcium metabolism suppression by calmodulin inhibitors correlates with the degree of inhibition of the aorta contractile response to serotonin. It was demonstrated that the inhibitory action of calmodulin antagonists on calcium metabolism in smooth muscle cells and the contractility of the isolated rat aorta during the activation of serotonin vasoconstrictive receptors are realized by a TRPV1-independent mechanism. It was demonstrated in experiments in vivo that trifluoperazine does not influence hypotensive reaction in rats (normally observed in response to intravenous serotonin injection), but removes the hypertensive effect of this neurotransmitter in rats after chronic introduction of dexamethasone. The results obtained confirm the hypothesis (that we previously stated) about the direct involvement of calmodulin in signal transmission from vasoconstrictive serotonin receptors.     

Effect of L-adrenaline on extracellular space in rabbit aorta and pulmonary artery]

Adrenaline causes an increase of extra-cellular fluid space in aorta and pulmonary artery of the rabbit. The effect is parallel in both tissues and the relative increase is about 20% of the normal value. The results confirm the oedematous reaction of the arterial wall to adrenaline; this action of adrenaline appears to be very long.     

慢性间歇性低压低氧对大鼠动脉血管收缩功能的影响

本研究旨在探讨慢性间歇性低压低氧(chronicintermittent hypobaric hypoxia,CIHH)对大鼠胸主动脉和肺动脉收缩功能的影响及其机制.雄性Sprague-Dawley大鼠随机分为4组:CIHH处理14天组(CIHH 14)、28天组(CIHH 28)、42天组(CIHH 42)和对照组(...     

Age-related changes of elements in thoracic and abdominal aortas and coronary, common carotid, pulmonary, splenic, common iliac, and uterine arteries and relationships in elements among their arteries

To elucidate whether the accumulation of elements occurred simultaneously in the various arteries with aging, the authors investigated age-related changes of elements in the eight arteries, such as the thoracic and abdominal aortas and the coronary, common carotid, pulmonary, splenic, common iliac, and uterine arteries, and the relationships in the element contents among their arteries. After ordinary dissection by medical students was finished, the thoracic and abdominal aortas and the coronary, common carotid, pulmonary, splenic, common iliac, and uterine arteries were resected from the subjects, who ranged in age from 58 to 94 yr. The element contents were analyzed by inductively coupled plasma-atomic emission spectrometry. It was found that the accumulation of Ca was the highest in the common iliac artery and decreased in the order of the uterine artery, abdominal aorta, coronary artery, thoracic aorta, splenic artery, common carotid artery, and pulmonary artery. Regarding the relationships in the element contents among the eight arteries, it was found that there were significant direct correlations in the contents of Ca, P, Mg, Zn, Fe, and Na between the coronary and splenic arteries, and there were significant correlations in the contents of Ca, P, and Mg between the abdominal aorta and pulmonary artery.