Peroxynitrite-induced relaxation in isolated rat aortic rings and mechanisms of action

The present study was designed to evaluate the effects of peroxynitrite (ONOO-), the product of superoxide and nitric oxide, on isolated segments of rat aorta. In the absence of any vasoactive agent, ONOO- (from 10(-8) to 10(-4) M) failed to alter the basal tension. In phenylephrine (PE; 5 x 10(-7) M)-precontracted rat aortic rings (RAR), ONOO- elicited concentration-dependent relaxation at concentrations of from 10(-8) to 10(-4) M. The effective concentrations producing approximately 50% of maximal relaxation (ED50) to ONOO- were 1.84 x 10(-5) M and 1.96 x 10(-5) M in intact and denuded RAR, respectively (P > 0.05). No significant differences in the relaxation responses were found between RAR with or without endothelium (P > 0.05). The presence of either 5 microM methylene blue (MB) or 5 microM 1H-[1,2,4]oxadiazolo-[4,3-alpha]quinoxalin-1-one (ODQ) significantly inhibited the relaxations induced by ONOO-. Sildenafil (10(-7) M), on the other hand, significantly potentiated the ONOO--induced relaxations. Tetraethylammonium chloride (T-2265) significantly decreased the ONOO--induced relaxations in a concentration-dependent manner. However, ONOO- had no effect on RAR precontracted by high KCL (40 mM, n = 6, P > 0.05). Addition of calyculin A also significantly decreased the ONOO--induced relaxation in a dose-dependent manner. Furthermore, ONOO- significantly inhibited calcium-induced contractions of K+-depolarized aortic rings in a concentration-related manner. Lastly, a variety of other pharmacological agents and antagonists including L-NMMA, L-arginine, indomethacin, atropine, naloxone, diphenhydramine, cimetine, glibenclamide, haloperidol, superoxide dismutase (SOD), and catalase did not influence the relaxant effects of ONOO- on RAR. Our new results suggest that ONOO--triggered relaxation on rat aortic rings is mediated by elevation of cGMP levels, membrane hyperpolarization via K+-channel activation, activation of myosin phosphatase activity, and interference with calcium movement and cellular membrane Ca2+ entry.     

黄芪甲苷对正常大鼠离体血管功能的影响

目的观察黄芪甲苷对血管功能的影响并探讨其作用机制。方法采用大鼠离体主动脉环灌流模型,观察黄芪甲苷对血管环收缩和舒张功能的影响。结果黄芪甲苷能够浓度依赖性舒张血管。一氧化氮合酶抑制剂、鸟苷酸环化酶及环加氧酶抑制剂可抑制黄芪甲苷诱导的血管舒张作用。黄芪甲苷能够抑制苯肾上腺、KC l和CaC l2引起的血管收缩。结论黄芪甲苷具有内皮依赖性的舒张血管作用,此作用主要通过NO-cGMP途径发挥作用。黄芪甲苷抑制血管收缩主要通过拮抗外钙内流实现。     

Cocaine-induced relaxation of isolated rat aortic rings and mechanisms of action: possible relation to cocaine-induced aortic dissection and hypotension

Cocaine HCl is well known for its toxic effects on the cardiovascular system, but little is known about its effects on different regional blood vessels. We designed experiments to determine if cocaine HCl could influence the tension of isolated aortic rings, i.e., induce contraction or relaxation. Surprisingly, cocaine HCl (1 x 10(-5) to 6 x 10(-3) M) relaxed isolated aortic rings precontracted by phenylephrine in a concentration-dependent manner. No significant differences were found between intact or denuded isolated aortic rings (P>0.05). The maximal % relaxations of intact vs. denuded isolated aortic rings were 108.9+/-24.3% vs. 99.5+/-8.3% (P>0.05). Cocaine HCl, 2 x 10(-3) M, was found to inhibit contractions by phenylephrine; EC50s were increased (P<0.01) and Emax's were decreased (51.3+/-16.4% vs. 89.8+/-10.6%, P<0.01). A variety of amine antagonists could not inhibit the relaxant effects of cocaine HCl (P>0.05). The cyclooxygenase-1 inhibitor, indomethacin, also failed to inhibit relaxations induced by cocaine HCl (P>0.05). Neither L-arginine, NG-monomethyl-L-arginine (L-NMMA), nor methylene blue could inhibit the relaxations induced by cocaine HCl (P>0.05), suggesting cocaine HCl does not relax isolated aortic rings by inducing the synthesis or release of nitric oxide (NO) or prostanoids from either endothelial or vascular muscle cells. Inhibitors of cAMP, cGMP and protein kinase G (PKG) also failed to inhibit cocaine-induced relaxations. Cocaine HCl (1 x 10(-5) to 6 x 10(-3) M) could also relax isolated aortic rings precontracted by phenylephrine in high K+ depolarizing buffer. Surprisingly, calyculin A, an inhibitor of myosin light chain (MLC) phosphatase, inhibited cocaine-induced relaxations in a concentration-dependent manner, suggesting the probable importance of cocaine-induced MLC phosphatase activation in rat aortic smooth muscle cells. It was also found that cocaine HCl could dose-dependently inhibit Ca2+-induced contractions of isolated aortic rings in high K+-Ca2+-free buffer, suggesting that cocaine HCl may inhibit Ca2+ influx and/or intracellular release.     

Increased nitroglycerin-induced relaxation by genistein in rat aortic rings.

The effect of genistein, a tyrosine kinase inhibitor, on nitroglycerin-induced relaxation was examined in rat aortic rings contracted by phenylephrine. In rat aortic rings, genistein (10(-5) M and 3x10(-5) M), a tyrosine kinase inhibitor, but not daidzein, an analogue of genistein, increased relaxation induced by nitroglycerin in a concentration-dependent manner. Iberiotoxin, an inhibitor of Ca2+ -activated K+ channels, inhibited the relaxation induced by nitroglycerin, but it did not affect the effect of genistein. Glibenclamide, an inhibitor of ATP-sensitive K+ channels, did not affect the relaxation induced by nitroglycerin. Theophylline, an inhibitor of cyclic AMP-dependent phosphodiesterase, increased the relaxation induced by nitroglycerin, and genistein (10(-5) M) failed to affect the relaxation induced by nitroglycerin in the presence of theophylline. Genistein also inhibited the activity of cyclic AMP-dependent phosphodiesterase. In addition, 6-[4-(4'-pyridyl)amino phenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride, an inhibitor of cyclic GMP-inhibitable cyclic AMP phosphodiesterase, inhibited the relaxation induced by nitroglycerin. These results suggest that, in the rat aortic rings, genistein inhibits cyclic AMP-dependent phosphodiesterase activities, resulting in the increase of the relaxation induced by nitroglycerin.     

Ambient particulate matter induces relaxation of rat aortic rings in vitro

Epidemiological studies have shown an association between ambient levels of particulate matter (PM) and increased mortality from cardiovascular diseases. However, the underlying mechanisms are still not clear. We hypothesised that PM, when translocated after inhalation, could affect vascular smooth muscle function. Therefore, total suspended particulate matter (TSP) was sampled and investigated for its ability to affect aortic muscle contraction. Both TSP and TSP supernatant (TSP-sup) induced a concentration-dependent relaxation of phenylephrine (PE)-precontracted aortic rings. Relaxation induced by 100 microg/ml TSP was 51.5 +/- 3.1% of total contraction. At 60 and 100 microg/ml, relaxation induced by TSP was significantly higher compared to TSP-sup. Ultrafine TiO2, used as a model to investigate the role of ultrafine particles, did not show an effect. Soluble iron, present in TSP suspensions, seems not to be involved, as chelating with deferoxamine did not affect TSP-induced relaxation. However, TSP effects were inhibited by Trolox, suggesting a role of oxidants. Nudation of aortic rings showed that effects of TSP were only partly endothelium-dependent, while preincubation with L-NAME increased TSP-induced relaxation. From these data, we conclude that both the particle core and soluble components of TSP can affect the smooth muscle function, leading to changes in the vascular contractile response.     

Kallikrein rK10-induced kinin-independent, direct activation of NO-formation and relaxation of rat isolated aortic rings.

1. rK10, a weak T-kininogenase isolated from the rat submandibular gland, is a protein belonging to the rat kallikrein family. In the present work, we have studied the biological effects of rK10 with respect to its ability to alter vascular resistance, either directly like rK9, i.e. another kallikrein-like protein, trypsin and thrombin, or through the release of kinins like tissue kallikrein (rK1). The direct effect was studied by its vasomotor activity on rat isolated aortic rings since this preparation was insensitive to the action of kinins. Its ability to induce altered vascular resistance through kinin-generation was investigated by blood pressure studies in whole animals. The studies were performed in comparison to rK1. 2. Unlike rK1, which induces hypotension when administered intravenously to rats (delta BP = -56 +/- 5 mmHg, 5 micrograms kg-1), rK10 did not have any effect on systemic blood pressure (delta BP = -3 +/- 1, 5 micrograms kg-1, i.v.). 3. rK10 was without effect on uncontracted aortic rings, but showed a concentration-dependent (10(-8)-10(-6) M) relaxant effect on tissue precontracted with phenylephrine (10(-6) M). After removal of endothelial cells, no relaxation was observed. The relaxant response to rK10 was transient. rK1 (with and without endothelium), bradykinin and T-kinin (with endothelium) had no effect on contracted or uncontracted aortic rings. 4. The relaxant effect of rK10 was dependent on its enzymatic activity since preincubation with aprotinin (1.02 mM) significantly reduced vasorelaxation from 74 +/- 4% to 24 +/- 3%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endothelium-dependent and -independent relaxation induced by pinocembrin in rat aortic rings

The aim of present study was to evaluate the vasorelaxant effects of the flavonone pinocembrin and its possible mechanisms in isolated rat aortic rings. Pinocembrin (5 approximately 100 microM) induced relaxation in aortic rings pre-contracted with norepinephrine (NE, 1 microM) or KCl (60 mM), with pEC(50) value 4.37+/-0.02 and 4.52+/-0.04. Pretreatment with pinocembrin (30 or 50 microM) also inhibited contractile responses to NE and KCl. The vasorelaxant effect of pinocembrin relied on intact endothelium partially, and incubation with n(omega)-nitro-l-arginine methyl ester (l-NAME, 100 microM) or methylene blue (10 microM) significantly inhibited the effect, however indomethacin (5 microM) had no influence on the action. In endothelium-denuded rings, the vasorelaxant effect of pinocembrin was reduced by glibenclamide (10 microM), tetraethylammonium (5 mM) and 4-aminopyridine (100 microM). Pinocembrin also reduced NE-induced transient contraction in Ca(2+)-free solution and inhibited contraction induced by increasing external calcium in Ca(2+)-free medium plus 60 mM KCl. Our results suggest that pinocembrin induces relaxation in rat aortic rings through an endothelium-dependent pathway, involving NO-cGMP, and also through an endothelium-independent pathway, opening K(+) channels and blockade of Ca(2+) channels.     

Phorbol esters impair endothelium-dependent and independent relaxation in rat aortic rings

• 1.1. This study examined the ability of various nitro-vasodilators, 8-bromo cyclic guanosine 3′:5′ monophosphate (8-BrcGMP) and forskolin to relax rings of rat thoracic aorta pre-contracted with either noradrenaline (0.1 μM) or the protein kinase C activators, phorbol 12,13-dibutyrate (PDB, 0.1 μM) or phorbol 12-myristate 13-acetate (PMA, 0.5 μM).
• 2.2. In noradrenaline pre-contracted rings, acetylcholine (10 nM−10 μM), sodium nitroprusside (1 nM−0.5 μM), the calcium ionophore A23187 (10 nM−10 μM) and 8-BrcGMP (10 mM) totally reversed the smooth muscle contraction. In PDB-contracted aortic rings acetylcholine, sodium nitroprusside and 8-BrcGMP-induced relaxation was reduced compared to that in noradrenaline-contracted aortic rings, but A23187 and forskolin-induced relaxations were unaffected. Both acetylcholine and A23187-induced relaxations in PDB-contracted rings were abolished in the presence of the nitric oxide synthesis inhibitor Nω-nitro-l-arginine (NOLA, 100 μM).
• 3.3. Acetylcholine and sodium nitroprusside were even less potent in their ability to relax PMA-contracted aortic rings compared with noradrenaline and PDB-contracted rings. A23187-induced relaxation was also inhibited in PMA-contracted rings.
• 4.4. These results show that protein kinase C activation reduces the ability of agents which liberate nitric oxide to induce smooth muscle relaxation, and also inhibits the biochemical pathways which are subsequently activated by nitric oxide and lead to vascular smooth muscle relaxation.

     

The potentiation of nitroglycerin-induced relaxation by PKG inhibition in rat aortic rings

• 1.1. In rat aortic rings precontracted by phenylephrine, H7 (10⁻⁵M) and staurosporine (10⁻⁷M), which inhibit PKA, PKG and PKC, and H-89 (10⁻⁶M), which inhibits PKA and PKG, potentiated relaxations induced by nitroglycerin. Forskolin-induced relaxations were not affected by H7 (10⁻⁵M).
• 2.2. Nitroglycerin-induced relaxations were not affected by calphostin-C (10⁻⁷M), which inhibits PKC, H-89 (10⁻⁷M), which inhibits PKA, and staurosporine (2 × 10⁻⁹M), which inhibits PKC.
• 3.3. Iberiotoxin (3 × 10⁻⁸M), an inhibitor of large conductance Kca channels, partly inhibited the relaxation induced by nitroglycerin and completely inhibited the potentiating effect of H7 on nitroglyc. erin-induced relaxations.
• 4.4. The potentiating effect of zaprinast (10⁻⁵M), an inhibitor of cGMP-phosphodiesterase, on nitroglycerin-induced relaxation was not affected by iberiotoxin. In the presence of methylene blue (10⁻⁵M), an inhibitor of guanylate cyclase, the residual relaxing response to nitroglycerin was not affected by H7, but it was inhibited by iberiotoxin.
• 5.5. These results suggest that the potentiation of nitroglycerin-induced relaxation by H7, staurosporine and H-89 may be due to inhibition of PKG.

     

Captopril restores endothelium-dependent relaxation of rat aortic rings after exposure to homocysteine

This study was designed to investigate the effects of captopril, an angiotensin-converting enzyme inhibitor, on inhibition of endothelium-dependent relaxation induced by homocysteine in isolated rat aorta. Isometric tension recordings were used to assess inhibitory effects of homocysteine and protective effects of captopril on endothelium-dependent relaxation of aortic rings. Exposure of aortic rings to homocysteine (0.3 approximately 3 mmol/L) for 30 min induced a significant concentration-dependent inhibition of endothelium-dependent relaxation response to acetylcholine (ACh), but did not affect endothelium-independent relaxation response to sodium nitroprusside. Pre-incubation of aortic rings with captopril (3 approximately 30 micromol/L) for 15 min and co-incubation of aortic rings with homocysteine (1 mmol/L) for another 30 min attenuated the inhibition of homocysteine in a dose-dependent manner. Moreover, superoxide dismutase (SOD, 200 U/mL), a scavenger of superoxide anions, reduced homocysteine-induced inhibition. L-Arginine (3 mmol/L), a precursor of nitric oxide (NO), also attenuated the impairment of vasorelaxation induced by homocysteine. However, in the combined presence of SOD and L-arginine, the inhibitory effect of homocysteine was reversed, which was very similar to the effect of 30 micromol/L captopril. These results suggest that captopril can prevent the inhibition of endothelium-dependent relaxation induced by homocysteine in isolated rat aorta, which may be related to scavenging oxygen free radicals and enhancing NO production.     

麝香保心丸对大鼠离体主动脉环的药理作用

目的：研究麝香保心丸的舒张血管作用及可能的机制。方法：将离体大鼠动脉环随机分成正常组，去内皮组２组（共为６对动脉环，组内比较用自身对照，组间比较用配对对照）。用去甲肾上腺素诱导动脉环收缩后，加入麝香保心丸，记录反应。结果：麝香保心丸对正常组，去内皮组动脉环均有舒张作用（Ｐ＜０．０１），其效应呈剂量依赖；且其对正常组的舒张作用较去内皮组强（Ｐ＜０．０１）。结论：麝香保心丸具有舒张血管的效应，其机制可能有直接及内皮依赖的舒张血管２种作用。     

L-citrulline mediated relaxation in the control and lipopolysaccharide-treated rat aortic rings.

The present study was undertaken to investigate relaxant effect of L-citrulline in phenylephrine precontracted endothelium intact thoracic aortic rings obtained from control or lipopolysaccharide (1 mg/kg)-treated rats. L-citrulline produced 40+/-3% (n=36) and 60+/-5% (n=24) relaxations in control and lipopolysaccharide-treated rings, respectively. Nitric oxide (NO) release and cyclic guanosine-3',5'-monophosphate levels from the rings were also increased following treatment with L-citrulline. Inhibition of guanylate cyclase, L-citrulline recycling to L-arginine or denudation of the endothelium, significantly reduced L-citrulline-induced relaxations both in control and lipopolysaccharide-treated rings. Treatment of rings with protein synthesis inhibitors prevented relaxations to L-citrulline. Inhibitor of Ca2+-activated K+ channels, tetrabutylammonium or precontraction of the rings with KCl (80 mM), significantly attenuated L-citrulline mediated relaxations in control and lipopolysaccharide-treated rings. Thus, L-citrulline seems to exert significant relaxation by supplementing the release of NO due to its recycling to L-arginine, which gets further augmented after lipopolysaccharide treatment.     

对氯苄基四氢小檗碱对正常及甲状腺功能亢进大鼠离体主动脉环的作用

研究对氯苄基四氢小檗碱(CPU-86017)对去氧肾上腺素(Phe)所致大鼠主动脉环收缩的影响. 作正常大鼠主动脉环在有钙或无钙K-H液，及左甲状腺素所致甲亢大鼠主动脉环在无钙K-H液中Phe累积浓度-收缩曲线，CPU-86017对上述条件下的主动脉环收缩均有抑制，使量效曲线右移，最大收缩力降低，pD₂′分别为4.12，6.08和4.33. 结果提示CPU-86017对受体操纵性Ca²⁺通道的阻滞作用强于对电压依赖性Ca²⁺通道的阻滞作用, 甲亢使细胞内Ca²⁺ 释放增多, CPU- 86017作用因此减弱.     

The vasorelaxing effect of hydrogen sulfide on isolated rat aortic rings versus pulmonary artery rings

Aim:

To compare the vasorelaxing effects of hydrogen sulfide (H₂S) on isolated aortic and pulmonary artery rings and to determine their action mechanisms.

Methods:

H₂S-induced vasorelaxation of isolated rat aortic versus pulmonary artery rings under 95% O₂ and 5% CO₂ was analyzed. The expression of cystathinonine gamma-lyase (CSE), cystathionine beta synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3MST), SUR2B and Kir6.1 was examined.

Results:

NaHS caused vasorelaxation of rat aortic and pulmonary artery rings in a dose-dependent manner. NaHS dilated aortic rings to a greater extent (16.4%, 38.4%, 64.1%, 84.3%, and 95.9% at concentrations of 50, 100, 200, 500, and 1000 μmol/L, respectively) than pulmonary artery rings (10.1%, 22.2%, 50.6%, 73.6%, and 84.6% at concentrations of 50, 100, 200, 500 and 1000 μmol/L, respectively). The EC₅₀ of the vasorelaxant effect for aortic rings was 152.17 μmol/L, whereas the EC₅₀ for pulmonary artery rings was 233.65 μmol/L. The vasorelaxing effect of H₂S was markedly blocked b y cellular and mitochondrial membrane K_ATP channel blockers in aortic rings (P<0.01). In contrast, only the cellular membrane K_ATP channel blocker inhibited H₂S-induced vasorelaxation in pulmonary artery rings. SUR2B mRNA and protein expression was higher in aortic rings than in pulmonary artery rings. Cystathinonine gamma-lyase (CSE) but not cystathionine beta synthase (CBS) expression in aortic rings was higher than in pulmonary artery rings. 3-Mercapto pyruvate sulfurtransferase (3MST) mRNA was lower in aortic rings than in pulmonary artery rings.

Conclusion:

The vasorelaxing effect of H₂S on isolated aortic rings was more pronounced than the effect on pulmonary artery rings at specific concentrations, which might be associated with increased expression of the K_ATP channel subunit SUR2B.     

对氯苄基四氢小檗碱对正常及甲状腺功能亢进大鼠离体主动脉环的作用

研究对氯苄基四氢小檗碱（ＣＰＵ－８６０１７）对去氧肾上腺素（Ｐｈｅ）所致大鼠主动脉环收缩的影响．作正常大鼠主动脉环在有钙或无钙Ｋ－Ｈ液,及左甲状腺素所致甲亢大鼠主动脉环在无钙Ｋ－Ｈ液中Ｐｈｅ累积浓度－收缩曲线,ＣＰＵ－８６０１７对上述条件下的主动脉环收缩均有抑制,使量效曲线右移,最大收缩力降低,ｐＤ２′分别为４．１２,６．０８和４．３３．结果提示ＣＰＵ－８６０１７对受体操纵性Ｃａ２＋通道的阻滞作用强于对电压依赖性Ｃａ２＋通道的阻滞作用,甲亢使细胞内Ｃａ２＋释放增多,ＣＰＵ－８６０１７作用因此减弱     

Histamine relaxation of aortic rings from diabetic rats

The effect of histamine-induced relaxation on thoracic aortic rings from rats 5, 12, 24 and 52 weeks following streptozotocin-induced diabetes was determined. Preliminary studies confirmed the dependence of histamine-induced relaxation and the independence of nitroglycerin-relaxation (GTN) on the presence of endothelium (EDRF). Diabetes was confirmed by blood glucose levels exceeding 300 mg/dl. Rings with endothelium were depolarized several times with 50 mM KCL and then contracted with phenylephrine (10(-6)). Dose-response curves were plotted from data obtained following exposure to histamine (10(-7)-10(-3)) and GTN (10(-9)-10(-7)) and compared to responses from age-matched untreated controls, diabetic and diabetic rats treated with insulin (2 U/day). The relaxation produced by histamine on phenylephrine pre-contracted rings was similar in all three groups from 5-week age matched rats. However, histamine-induced relaxation from untreated diabetic rats was significantly depressed at 12, 24 and 52 weeks (p less than 0.001). Conversely there was no difference in the relaxation elicited by GTN on rings obtained from the three groups at any age. Pretreatment with diphenhydramine (5 x 10(-7)) on aortic rings from 12 and 52-week age matched rats resulted in qualitatively similar histamine dose-response curves that were displaced about two orders of magnitude to the right, indicative of H1 receptor competitive antagonism. These results demonstrate that the duration of diabetes alters the responsiveness of rat thoracic aortic rings to histamine but not to GTN and suggests that the responses elicited by certain agonists on target tissues may be significantly altered depending on the duration of diabetes.     

Mechanisms underlying vasorelaxant action of astragaloside IV in isolated rat aortic rings

1. Astragaloside IV is a component from the widely used traditional Chinese herb Astragalus membranaceus and its effect on rat aortic ring contraction and relaxation were investigated. 2. The aorta from male Sprague-Dawley rats was isolated in an organ bath and ring tension was recorded with or without endothelium. Cumulative effects of astragaloside IV on vessel contraction and relaxation were observed in the presence of various antagonists related to vessel activity. 3. Astragaloside IV showed concentration-dependent inhibition of vessel contraction induced by phenylephrine and potassium chloride. The amount of calcium released from intracellular stores sensitive to phenylephrine was also markedly reduced by astragaloside IV. There was dose-dependent vasorelaxation in endothelium-intact rings, which was partly inhibited by pre-incubation with nitric oxide (NO) synthase (NOS) Nomega-nitro-L-arginine methyl ester and guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazolo [4,3-alpha] quinoxalin-1-one. Astragaloside IV also induced a significant increase in aortic tissue content of guanosine 3",5"-cyclic monophosphate (cGMP) both in vivo and in vitro. Endothelial NOS inhibitor Nomega-nitro-L-arginine prevented vasodilatation, whereas neuronal NOS inhibitor 7-nitroindazole did not show significant influence on the vessel relaxation of astragaloside IV. 4. In conclusion, astragaloside IV inhibited vessel contraction through blocking calcium influx and intracellular calcium release. The endothelium-dependent vessel dilation of astragaloside IV was attributed mainly to the endothelium-dependent NO-cGMP pathway.     

胍法新对保存内皮与去内皮离体大鼠胸主动脉环的作用

本实验观察了选择性较高的α_2受体激动剂胍法新(guanfacine)对离体大鼠胸主动脉环的收缩与舒张作用和对血管组织中cGMP含量的影响。去内皮以及用美兰和血红蛋白预处理均可使胍法新对标本的收缩作用明显增强。对经垂体后叶素预收缩的保存内皮的标本,胍法新有舒张作用。这种作用可因去内皮或用育亨宾处理而消失。胍法新使保存内皮标本组织中cGMP含量明显增加。这些结果提示在大鼠胸主动脉内皮细胞上可能存在着能引起EDRF释放的α_2受体。     

Vasorelaxant effects of Acer nikoense extract and isolated coumarinolignans on rat aortic rings

The organic extract of the heartwood of Acer nikoense Maxim. (Aceraceae) showed vasorelaxant activity on rat aorta with or without endothelium. Coumarin [scopoletin (1)] and coumarinolignans [cleomiscosin A (2) and aquillochin (3)] were isolated as major constituents from the organic extract of the heartwood of A. nikoense. Compounds 1-3 exhibited moderate vasorelaxant effects on rat aorta, while 2 and 3 showed vasorelaxant effects in the norepinephrine-stimulated and also in high K+-depolarized preparations.     

吗啉环和哌嗪环类新衍生物对血管舒张功能的影响

目的　利用ETA与M受体的相似性和差异性 ,设计合成吗啉环和哌嗪环类新结构化合物 ,分析其对血管舒张功能的影响。方法　采用离体大鼠胸主动脉环 ,观察化合物对血管张力的影响 ;并观察L NAME ,吲哚美辛和阿托品对血管环最大舒张率的影响。结果　 81个化合物中有 57个能舒张血管 ,其中 8个最大舒张率在 50 %～ 85 % ;活性化合物按母核可分为 8类 ;DMHPPP和PPVP诱发的内皮依赖性舒血管反应可被L NAME和吲哚美辛所拮抗 ,但不被阿托品拮抗 ;DMHPPP和PPVP还能显著增强乙酰胆碱 (ACh)诱发的内皮依赖性舒血管反应的最大舒张率。结论　具有舒血管作用的活性化合物通过促进内皮细胞释放一氧化氮(NO)和前列环素 (PGI2 )共同实现舒张效应 ;并可调节血管内皮细胞乙酰胆碱靶标的功能