心房肽Ⅲ对人体血管作用的差异性

采用离体人脐动脉,人胃网膜右动脉,家兔及大白鼠胸主动脉肌条,观察APⅢ和NP的作用。APⅢ75nmol/l对由NA3μmol/l,5-HT1μmol/l,HT10μmol/l,PE 1μmol/l收缩的家兔及大白鼠胸主动脉肌条具有明显松弛作用,对由上述药物及KCl 80mmol/l,PGF_(2α)10μmol/l所收缩的人脐动脉及人胃网膜右动脉并无松弛作用。NP 1μmol/l对由NA3μmol/l,5-HT 1μmol/l,HT 10μmol/l等所收缩的两种人血管都有明显松弛作用,并能降低血管基本张力。结果提示:APⅢ对家兔及大白鼠的胸主动脉有松弛作用,但对人脐动脉及人胃网膜右动脉无松弛作用,表明APⅢ对血管的作用可能具有动物种属或血管种类差异性,NP则有较普遍的血管松弛作用。     

前胡丙素对豚鼠心房和兔主动脉条的钙拮抗作用

前胡丙素(Pra—C)非竞争性抑制CaCl_2和高钾除极化所致兔主动脉条的收缩,pD’_2值分别为4.9和5.0;抑制5—HT诱导的依外钙性收缩,但不影响依内钙性收缩及NE诱导的收缩;Pra—C5～50μmol/L浓度依赖性地抑制豚鼠左房收缩力和阶梯现象;Pra—C抑制血管与心脏的IC_(50)之比为1:8。结果提示Pra—C对血管和心脏的抑制作用可能与拮抗Ca~(2+)有关,且主要影响经PDCs的外钙内流。     

高血压对大鼠脑基底动脉收缩和钠泵活性的影响

目的探讨高血压对大鼠脑血管收缩性的影响及其与钠泵活性的关系。方法取♂Wistar大鼠(WR)和自发性高血压大鼠(SHR)基底动脉环,通过Multi Myograph张力换能系统记录血管张力变化,比较两种大鼠离体脑动脉对KCl和5-羟色胺(5-HT)的收缩反应,分析高血压病变对脑血管收缩性和钠泵活性的影响。结果与WR基底动脉相比,SHR基底动脉的KCl和5-HT量效曲线明显右移,再复K+所致血管舒张作用减弱,提示高血压病变可明显降低脑血管钠泵活性及KCl和5-HT的收缩反应;哇巴因(Ouabain,OUA)浓度依赖性收缩SHR脑血管,其量效关系曲线可经两点结合模型进行最佳拟合,Kd分别为:1.7×10~(-8)mol·L~(-1)和1.6×10~(-5)mol·L~(-1),表明SHR脑基底动脉上存在高、低亲和力两种不同功能的钠泵。用5×10~(-7)mol·L~(-1)和10~(-4)mol·L~(-1)的OUA分别抑制高、低亲和力钠泵,仅能在SHR而非WR脑血管明显左移KCl和5-HT量效曲线,表明OUA可明显增强KCl和5-HT对脑血管的收缩作用,且OUA增强5-HT收缩SHR脑血管的作用呈明显的浓度依赖性(r=0.9393,P<0.05);在SHR脑血管,这两个浓度OUA对KCl量效曲线的左移幅度无明显差别,而对5-HT收缩量效曲线的左移幅度却有明显不同,提示仅高亲和力钠泵介导了SHR脑血管对KCl的收缩反应,而SHR脑血管对5-HT的收缩反应则由高、低亲和力两种钠泵共同参与。结论高血压病变可明显降低脑血管对血管收缩剂的反应性,其机制可能与高血压所致钠泵活性降低或钠泵对OUA敏感性增加有关。     

参麦注射液对大鼠离体胸主动脉血管环作用及机制的研究

目的 探讨参麦注射液对离体大鼠胸主动脉血管环的作用及作用机制.方法 采用离体血管灌流方法,观察参麦注射液对血管环的直接作用;对苯肾上腺素(PE)或氯化钾(KCl)所引发收缩作用的影响;对内钙释放和外钙内流所引发收缩作用的影响;对乙酰胆碱(ACH)所引发舒张作用的影响.结果 参麦注射液对血管环无明显的直接作用(与对照组比较P均＞0.05);对PE和KCl引发的收缩均有明显的抑制(与对照组比P＜0.05);对内钙释放和外钙内流所引发收缩作用均有明显的抑制(与对照组比较P均＜0.01);对ACH所引发的舒张作用有明显的抑制(与对照组比较P均＜0.05).结论 参麦注射液既能抑制PE和KCl对血管环所引起的收缩作用,又能抑制ACH对血管环所引起的舒张作用,有双向调节血管张力的作用.     

参麦注射液对大鼠离体胸主动脉血管环的作用及其机制

目的 探讨参麦注射液对大鼠离体胸主动脉血管环的作用及其机制。方法采用离体血管灌流方法，观察参麦注射液对血管环的直接作用；对苯肾上腺素(PE)或氯化钾(KCl)所引发血管收缩作用的影响；对内钙释放和外钙内流所引发血管收缩作用的影响；对乙酰胆碱(ACh)所引发血管舒张作用的影响。结果参麦注射液对血管环无明显的直接作用；对PE和KCl引发的收缩均有明显的抑制(P＜0.05或＜0.01)；对内钙释放和外钙内流所引发收缩作用均有明显的抑制(P＜0.01)；对ACh所引发的舒张作用有明显的抑制(P＜0.05或＜0.01)。结论参麦注射液既能抑制PE和KCl对血管环所引起的收缩作用，又能抑制ACh对血管环所引起的舒张作用，有双向调节血管张力的作用。     

大豆黄酮血管舒张作用与血管内皮的关系

目的研究植物雌激素大豆黄酮(daidzein,Dai)的舒张血管效应与血管内皮M受体,细胞内、外钙的关系。方法采用家兔离体主动脉环进行等长张力实验。结果Dai(3～100μmol·L-1)对苯肾上腺素(phenylephrine,PHE)依内Ca2+性收缩和依外Ca2+性收缩均具有显著的抑制作用;Dai(10～100μmol·L-1)可使KCl的量效曲线右移,最大效应降低;Dai(10～100μmol·L-1)对ACh引起的血管环的舒张反应有浓度依赖性的增强作用,且在用阿托品阻断M受体后Dai对KCl引起的收缩的舒张效应减弱。结论Dai舒张血管效应与抑制内Ca2+释放和外Ca2+内流有关;Dai对血管环的直接舒张作用与ACh相似,也是通过激动内皮上的M受体释放EDRF等而引起的,且具有内皮依赖性。     

牛磺酸对大鼠胸主动脉的舒张作用及其机制的研究

目的研究牛磺酸舒血管作用的可能机制。方法记录苯肾上腺素(PE)和KCl预收缩的离体大鼠主动脉环张力变化,观察牛磺酸的舒血管作用及不同工具药对其作用的影响。结果牛磺酸(20~80mmol.L-1)对PE(1μmol.L-1)或KCl(60mmol.L-1)预收缩的大鼠主动脉环均有非内皮依赖的、浓度依赖性的舒张作用。在内皮完整的血管环,左旋硝基精氨酸甲酯(0.1mmol.L-1)对牛磺酸的舒血管作用无明显影响;β-丙氨酸(60mmol.L-1)在PE预收缩的血管环增强牛磺酸的舒血管作用,而在KCl预收缩的血管环则降低牛磺酸的舒血管作用;在KCl预收缩基础上,钾通道阻断剂格列本脲(10μmol.L-1)和四乙胺(10mmol.L-1)明显抑制牛磺酸的舒血管作用,而4-氨基吡啶(1mmol.L-1)和BaCl2(1mmol.L-1)无影响。结论牛磺酸有浓度依赖性的血管舒张作用,此作用不依赖血管内皮,可能与其跨细胞膜转运有关,可能有钙依赖性钾通道和ATP敏感性钾通道的参与。     

氯通道阻断剂对KCl、5-HT引起的兔脑椎基底动脉血管环收缩效应的影响

目的　探讨不同种类氯通道阻断剂在不同激动剂引起的脑血管平滑肌收缩反应中的作用。方法　记录离体兔脑椎基底动脉环收缩反应。结果　①氯通道阻断剂DIDS、Furosemide及NPPB均浓度依赖性抑制高K+ 及 5 HT引起血管环收缩反应 ,DIDS、Furosemide及NPPB对 5 HT引起收缩的抑制作用明显强于对KCl的作用 ;②在 5 HT引起血管收缩反应中 ,给予SK&F96 36 5引起血管最大舒张的基础上 ,DIDS、Furosemide及NPPB均可引起血管进一步舒张。结论　氯通道可能参与了由高K+ 去极化和 5 HT引起的兔脑椎基底动脉环收缩反应     

二烯丙基三硫化物对大鼠离体肾内动脉血管张力的影响

目的观察二烯丙基三硫化物(diallyl trisulfide,DATS)对离体肾内动脉张力的影响及其机制。方法 SD大鼠体质量250～300 g,脱臼处死后,显微操作下取出肾内动脉,制备成1.8～2.0 mm长的血管条,每根血管条固定于微血管测定仪的浴槽内,记录张力变化。分别给予血管收缩剂苯肾上腺素(Phe)、血栓素A2受体激动剂(U46619)、5-羟色胺(5-HT)和KCl刺激血管产生持续性收缩,采用累积给药法加入DATS,观察不同浓度的DATS对肾内动脉张力的影响。观察DATS舒张效应的同时用等体积的药物溶剂二甲基亚砜(DMSO)作为对照。结果 DATS能呈浓度依赖性诱导舒张1μmol.L-1 Phe、0.1μmol.L-1 U46619和2μmol.L-1 5-HT预收缩内皮完整的肾内动脉环,pD2分别为(6.06±0.17),(6.14±0.26)和(5.37±0.16),其最大舒张率(Emax)分别为(91.24±2.71)%,(93.44±2.14)%和(92.51±1.15)%;但是,对60 mmol.L-1 KCl预收缩的肾内动脉环无明显舒张作用;分别用eNOS抑制剂L-NAME和sGC抑制剂ODQ预处理内皮完整的肾内动脉环不影响DATS舒张效应;去除肾内动脉血管内皮也不影响DATS对其舒张作用。结论 DATS有浓度依赖性舒张大鼠肾内动脉作用,无明显内皮依赖性。     

鸟苷对大鼠胸主动脉血管环的舒张作用及机制

目的研究鸟苷对大鼠离体血管环的影响,并探讨其可能的作用机制。方法分离SD大鼠胸主血管环,分成去内皮组和内皮完整组,采用离体血管环实验方法,经生物信号采集与分析系统测定血管环张力的变化,观察鸟苷的舒血管作用并探讨不同抑制剂对鸟苷舒张大鼠离体血管环作用的影响。结果鸟苷(10-9～10-5 mol.L-1)对基础状态下或KCl预收缩血管环的张力无影响;对PE预收缩的血管环有内皮依赖性舒张作用;环氧合酶抑制剂吲哚美辛孵育对鸟苷的舒张作用无明显影响;一氧化氮合酶抑制剂L-NAME或鸟苷酸环化酶抑制剂亚甲蓝可阻断鸟苷的血管舒张作用。结论鸟苷对大鼠离体胸主动脉有浓度依赖性舒张作用,其舒张作用可能与NO-GC-cGMP途径相关。     

多沙唑嗪对映体对兔离体膀胱逼尿肌的作用及机制

目的观察多沙唑嗪(rac-DOX)及其对映体(S-DOX、R-DOX)对兔离体膀胱逼尿肌的作用并分析其机制。方法制备兔背侧和腹侧膀胱逼尿肌标本,记录药物或神经刺激诱发的膀胱平滑肌收缩反应。结果在兔背侧和腹侧膀胱逼尿肌标本,卡巴胆碱产生浓度依赖性收缩反应,两种标本的收缩反应差异无显著性(P>0·05)。在背侧膀胱逼尿肌标本,苯肾上腺素产生浓度依赖性收缩反应;但是,苯肾上腺素对腹侧膀胱逼尿肌无作用。S-DOX、R-DOX和rac-DOX在1μmol·L-1时,均可竞争性拮抗苯肾上腺素诱发的兔背侧膀胱逼尿肌收缩反应,其pKB值分别为7·44±0·19、7·39±0·14和7·38±0·30,三者的pKB值相同。电场刺激诱发兔背侧和腹侧膀胱逼尿肌产生稳定的收缩反应,该收缩反应被0·3μmol·L-1浓度的河豚毒素完全阻断。S-DOX、R-DOX和rac-DOX均抑制电场刺激诱发的背侧膀胱逼尿肌收缩反应(P<0·01),且三者的抑制作用强度差异无显著性(P>0·05);但是,它们对电场刺激诱发的腹侧膀胱逼尿肌收缩反应无影响。结论在兔离体膀胱背侧逼尿肌,S-DOX拮抗苯肾上腺素诱发收缩反应的pKB值与rac-DOX和R-DOX相同,三者尚能抑制电场刺激诱发的神经源性收缩反应。     

POSSIBLE INTERACTION OF CHOLINERGIC NERVES WITH TWO DIFFERENT (PRE AND POST) SITES OF THE NEUROMUSCULAR JUNCTION IN GUINEA-PIG VAS DEFERENS

• 1 Effects of various drugs on the mechanical responses of the longitudinal smooth muscle of guinea-pig vas deferens evoked by ACh and field nerve stimulation were examined.
• 2 ACh (28–280, μM) produced a contraction consisting of two phases. The first phase of the contraction was suppressed by guanethidine and by nicotinic antagonists. The second phase was suppressed only by atropine. Both phases were unaffected by TTX or prazosin.
• 3 Field stimulation (0.1 msec, 40 Hz) evoked contractions which also consisted of two (early and late) phases. Guanethidine (0.1-1 μM) suppressed both phases whilst prazosin (1 μM) suppressed only the late phase.
• 4 Atropine (0.1 μM) suppressed both phases whilst physostigmine (5 μM) potentiated both phases of field stimulation-evoked contractions.
• 5 Pentolinium suppressed both phases of field stimulation-evoked contractions at low concentrations (2–10 μM), but potentiated them at a higher concentration (100 μM).
• 6 dTC at a low concentration (0.5 mUM) suppressed the early phase, but slightly enhanced the late phase of field stimulation responses. At a higher concentration (20 μM), dTC potentiated both phases of the response.
• 7 Pentolinium and dTC did not affect the contractions induced by 90 mM-K ions, ATP or NA.
• 8 These results suggest that cholinergic nerves possess an excitatory action not only directly at the smooth muscle but also at the noradrenergic nerve terminals. The role of each receptor is discussed further.

     

Mechanism of vasodilatory effect of berberine in rat mesenteric artery.

The aim of this experiment was to study the mechanism by which berberine inhibits phenylephrine-induced contractions in isolated mesenteric arteries. The results show that berberine (10(-7)-3 x 10(-5) M) induced a dose-dependent vasodilation, and that the vasorelaxant effect of berberine was attenuated by the removal of the endothelium. Two known inhibitors of endothelium-derived relaxing factor (EDRF), L-NG-nitro arginine (L-NOARG) (a specific inhibitor of nitric oxide formation from L-arginine) and methylene blue (an inhibitor of soluble guanylyl cyclase), significantly attenuated the vasodilator response to berberine. In addition, berberine, like other vasodilators, differently affected the phasic and tonic contractile response elicited by either phenylephrine or high potassium. Berberine (3 x 10(-7) M) significantly inhibited the phasic contraction induced by phenylephrine but, in contrast to verapamil, had no effect on the high potassium-induced contraction. Moreover, berberine abolished the caffeine-induced contraction in Ca(2+)-free/EGTA medium. In conclusion, berberine vasodilates the rat mesenteric artery in part by indirectly releasing EDRF but mainly by directly blocking the release of Ca2+ from internal stores.     

Effects of nipradilol on alpha-adrenoceptor function in ocular arteries

The effects of nipradilol, a drug used in the treatment of glaucoma, on the contractions induced by noradrenaline and phenylephrine in isolated dog central retinal, external and internal ophthalmic arteries and pig ciliary arteries were investigated. In dog ocular arteries treated with oxyhemoglobin (1.6 x 10(-5) mol/l) to adsorb nitric oxide, noradrenaline (2 x 10(-8) to 10(-5) mol/l) produced a concentration-related contraction which was markedly inhibited by prazosin but not by yohimbine. Nipradilol (10(-9) to 10(-7) mol/l) slightly but significantly inhibited the noradrenaline-induced contraction in a concentration-related manner, but the inhibitory potency and efficacy were much less than those of prazosin. However, nipradilol inhibited the phenylephrine-induced contraction with a similar PA(2) value of prazosin. In pig ciliary arteries treated with oxyhemoglobin, noradrenaline-induced contraction was slightly inhibited by prazosin but markedly inhibited by yohimbine. Nipradilol, similarly to timolol, did not inhibit, but rather tended to potentiate, the contraction elicited by noradrenaline. The contraction induced by phenylephrine was significantly inhibited by prazosin and nipradilol. It is concluded that nipradilol acts as an alpha(1)-adrenoceptor antagonist (but not as an alpha(2)-adrenoceptor antagonist) in the ocular arteries, which may partially explain its ocular-pressure-lowering mechanism. Taken together with the results of our previous studies, the potencies of the nipradilol-induced vascular actions in ocular arteries are found to be in the following order: beta-adrenoceptor inhibition > alpha(1)-adrenoceptor inhibition falling dots direct vasodilation via a release of nitric oxide.     

Thapsigargin-induced endothelium-dependent triphasic regulation of vascular tone in the porcine renal artery.

1. To elucidate the role of thapsigargin-induced Ca2+ entry in endothelial cells in the regulation of vascular tone, changes in Ca2+ and force of smooth muscle were simultaneously monitored in fura-2-loaded strips of porcine renal artery. 2. During phenylephrine-induced sustained contraction, thapsigargin caused an endothelium-dependent triphasic response; an initial relaxation, a subsequent transient contraction, and a sustained relaxation. The initial relaxation and the contraction were associated with a decrease and an increase in [Ca2+]i, respectively. There was no apparent [Ca2+]i decrease during the sustained relaxation. Thapsigargin-induced responses were observed at 10-8 M and higher concentrations, with the maximum response observed at 10-6 M. 3. The transient contraction was inhibited by a cyclo-oxygenase inhibitor (10-5 M indomethacin), a thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist (10-5 M ONO-3708), and a TXA2 synthase inhibitor (10-5 M OKY-046). 4. During the phenylephrine-induced contraction in the presence of indomethacin, thapsigargin caused an initial, but not a sustained relaxation, in the presence of Nomega-nitro-L-arginine methylester (L-NAME). During the contraction induced by phenylephrine plus 40 mM K+-depolarization in the presence of indomethacin, thapsigargin induced both a transient and a sustained relaxation. However, these relaxations were completely abolished in the presence of L-NAME. 5. Thapsigargin caused a large Ca2+ elevation in cultured endothelial cells of the renal artery. The concentration-response relation was thus similar to that for force development in the arterial strips. 6. In conclusion, thapsigargin-induced Ca2+ entry in endothelial cells led to triphasic changes in the tone of the porcine renal artery. The endothelium-dependent contraction was mediated mainly by TXA2. Nitric oxide and hyperpolarizing factor are both involved in the initial relaxation. However, a sustained relaxation was observed which mainly depended on nitric oxide.     

Involvement of Nitric Oxide in Fading of 5-Hydroxytryptamine-Induced Vasocontraction

Abstract: This investigation was done to determine whether vascular nitric oxide is involved in the fading of 5-hydroxytryptamine (5-HT)-induced contraction of isolated aortic strips from rats. The 5-HT (100 μM)-induced contractile response showed a gradual decrease in tension after a plateau level had been attained. The degree of the fadeaway was less in strips without endothelium than in those with endothelium. Pretreatment with nitro-L-arginine (100 μM) or haemoglobin (10 μM) suppressed the fadeaway of 5-HT contraction in both types of strips, although the effect was less in strips without endothelium. In contrast to 5-HT contraction, phenylephrine (10 μM) contraction in the presence of endothelium did not begin fading away for at least 1 hr after stimulation. In strips precontracted with 5-HT (100 μM), relaxation induced by sodium nitroprusside (1-50 nM) was significantly higher than in those precontracted with phenylephrine (10 μM). There was no significant difference between the cyclic GMP levels at 1 hr after stimulation with phenylephrine (10 μM) and 5-HT (100 μM). These results suggest that decrease in vascular tone in rat aorta after the plateau of 5-HT contraction has been reached is in part due to nitric oxide derived from vascular endothelial and non-endothelial cells. The vascular tone decreases more quickly after the plateau in the case of 5-HT contraction than of phenylephrine contraction, which may be due to higher sensitivity of 5-HT contraction to nitric oxide.     

Calcium antagonists inhibit positive chronotropic responses to alpha 1-adrenoceptor activation in rat isolated atria

Positive chronotropic responses of rat isolated atria to phenylephrine were reduced by propranolol (0.3 microM) and the residual response was further depressed by the selective alpha 1-adrenoceptor antagonist prazosin (1 nM) but not yohimbine (10 nM), confirming that a component of the response to phenylephrine was due to activation of alpha 1-adrenoceptors. When beta-adrenoceptors were blocked by propranolol, the positive chronotropic response to phenylephrine was enhanced by increasing the calcium concentration and by the calcium channel activator Bay K 8644 (0.1 microM), whereas the response was decreased by lowering the calcium concentration and by the calcium antagonists verapamil (10 nM), nifedipine (10 nM) and diltiazem (100 nM). In the presence of prazosin, when phenylephrine acts only on beta-adrenoceptors, calcium antagonists had no effect on the response. In rat isolated aortic strips in a calcium-free, high K+ (40 mM) solution, verapamil (10 nM), nifedipine (10 nM) and diltiazem (100 nM) shifted the calcium-induced contraction curves to the right, but prazosin (10 nM) had no effect, indicating that it is not a calcium antagonist. The calcium antagonists in the concentrations stated above had no effect on phenylephrine-induced contractions of rat aortic strips in normal Krebs-Henseleit solution, indicating that they did not block alpha 1-adrenoceptors in these concentrations. Taken together, these data suggest that the positive chronotropic effect of phenylephrine resulting from activation of alpha 1-adrenoceptors involves an increased influx of calcium through channels that are sensitive to organic calcium antagonists.     

α_1和α_2受体激动剂对家兔右心室乳头状肌动作电位和收缩力的影响

在普萘洛尔阻断β受体的情况下,苯福林延长动作电位时程(APD)和有效不应期(ERP),增强心肌收缩力;该作用可被哌唑嗪所拮抗。在利血平化的家兔右心室乳头状肌上,B-HT 920在较低浓度时,对动作电位及收缩力无显著影响;在较高浓度时,可明显延长APD和ERP,但B-HT 920的上述作用不能被育亨宾所拮抗。实验证明在家兔右心室乳头状肌上,突触后α受体的生理效应是由α_1受体介导的,本实验不能证实有功能性突触后α_2受体存在。     

巴马汀的α肾上腺素受体阻断作用

用大鼠肛尾肌、兔主动脉和门静脉条观察巴马汀(Pal)的α_1受体阻断作用,用大鼠输精管观察其α_2受体阻断作用。在前三种标本中,Pal的pA_2值分别为5.8,5.9,5.3;在大鼠输精管中,其pA_2值为5.1。Pal能分别降低[~3H]Pra及[~3H]CLN与大鼠脑细胞膜α_1及α_2受体的特异性结合量,竞争抑制常数K_I分别为4.53μM及2.0μM。提示Pal能竞争性阻断α_1和α_2的受体。