内皮的存在掩盖了邻苯三酚与亚甲蓝直接舒张大鼠肠系膜动脉的效应(英文)

在灌注的大鼠肠系膜血管,邻苯三酚与亚甲蓝能增强甲氧胺或电刺激释放去甲肾上腺素的缩血管效应。然而,当亚硝基精氨酸甲酯存在或去内皮时,两者可抑制TNS所致的缩血管效应,去除内皮后,邻苯三酚与亚甲蓝产生浓度依赖性舒血管效应,结果提示,血管内皮存在可能掩盖邻苯三酚与亚甲蓝两者的直接舒张血管平滑肌作用。     

邻苯三酚与亚甲蓝舒张大鼠肠系膜动脉的不同机制

在去内皮肠系膜血管，邻苯三酚与亚甲蓝产生浓度依赖性舒张，ＳＯＤ可取消禽苯三酚对ＴＮＳ所致缩血管效应的抑制作用，但不影响亚甲蓝的效应，邻苯三酚与亚甲蓝的舒血管效应不被过氧化氢酶，去铁胺，吲哚美辛和辣椒素所影响，结果提示，邻苯三酚的舒血管效应是其产生超氧阴离子所致，而亚甲蓝的效应为直接作用于血管平滑肌。     

内皮的存在掩盖了邻苯三酚与亚甲蓝直接舒张大鼠肠系膜动脉的效应

在灌注的大鼠肠系膜血管，邻苯三酚与亚甲蓝能增强甲氧胺或电刺激释放去甲肾上腺素的缩血管效应。然而，当亚硝基精氨酸甲酯存在或去内皮时，两者可抑制ＴＮＳ所致的缩血管效应。去除内皮后，邻苯三酚与亚甲蓝产生浓度依赖性舒血管效应。结果提示，血管内皮存在可能掩盖邻苯三酚与亚甲蓝两者的直接舒张血管平滑肌作用。     

川阿格雷钠舒张血管的作用及机制研究

目的:研究川阿格雷钠(MC-002)对大鼠胸主动脉的舒张作用,并探讨其可能的作用机制.方法:测定川阿格雷钠对去甲肾上腺素(NE)和高钾预收缩的大鼠胸主动脉血管环的舒张作用,并观察L硝基精氨酸甲酯(L-NAME)、亚甲蓝、吲哚美辛、格列本脲、蜂毒明肽、氯化钡和4-氨基吡啶对其作用的影响.结果:川阿格雷钠(3～300 μmol/L)能浓度依赖性地舒张NE预收缩的完整血管环,去内皮、亚甲蓝孵育和吲哚美辛孵育均能显著抑制其舒血管作用(P＜0.05,P＜0.01),L-NAME孵育无显著影响.川阿格雷钠拮抗高钾诱导完整血管环收缩的作用被格列本脲(ATP敏感型钾通道KATP抑制剂)和蜂毒明肽(小传导性钙激活型钾通道SKCa抑制剂)显著降低(P＜0.01),氯化钡和4-氨基吡啶无显著影响.川阿格雷钠使NE预收缩的血管平滑肌的钙浓度-收缩曲线下移、右移,且呈现浓度依赖性.结论:川阿格雷钠可能通过内皮细胞的鸟苷酸环化酶途径和环氧合酶途径、开放KATP和SKCa引起平滑肌细胞膜超极化以及减少钙内流而松弛血管.     

缬沙坦对尼古丁损伤血管内皮依赖性舒张功能的保护作用及机制

目的:探讨缬沙坦对尼古丁损伤大鼠肠系膜动脉内皮依赖性舒张反应的保护作用及机制。方法:将培养的成年SD大鼠肠系膜动脉环分为空白对照组(C组),尼古丁组(N组),缬沙坦低、中、高剂量组(V1、V2、V3组),吲哚美辛组(I组)和L-Nω硝基精氨酸甲酯组(L组)7个组。尼古丁组将血管环与0.1mmol/L尼古丁共同培养;缬沙坦组加入不同浓度(0.1、1、10μmol/L)缬沙坦与0.1mmol/L尼古丁,共同培养;吲哚美辛组和L组加入10μmol/L缬沙坦、0.1mmol/L尼古丁与10μmol/L吲哚美辛或100μmol/LL-Nω硝基精氨酸甲酯,共同培养。各组血管环均培养24h。培养后,应用离体血管环张力描记法,研究不同浓度的乙酰胆碱(ACh)对血管内皮依赖性舒张反应的影响。结果:除ACh浓度(10-9、10-8.5、10-7mol/L)外,大鼠的血管最大舒张率N组与C、V2、V3组,V3组与I组、L组之间差异均有统计学意义(P<0.05或P<0.01)。结论:缬沙坦可能通过促进内皮细胞释放一氧化氮和前列环素而发挥保护尼古丁对血管内皮依赖性舒张功能损伤的作用。     

TMB-8对大鼠软脑膜动脉收缩的作用(英文)

目的:研究TMB-8对大鼠软脑膜动脉的作用。方法:通过颅窗连续直接地观察软脑膜动脉,用微循环系统记录和分析动脉直径的变化。结果:Nim 1μmol·L~(-1)使PA直径立即增加,在给药后2min时达到最大,而TMB-8 50μmol·L~(-1)对PA无明显影响。预先给予TMB-825,50μmol·L~(-1)则明显抑制KCl引起的PA收缩幅度。在CSF中存在5-HT使PA持续收缩的情况下,TMB-8浓度依赖性地扩张PA,在TMB-8 50μmol·L~(-1)加入前,灌流一氧化氮(NO)合酶抑制剂L-NAME 10μmol·L~(-1)则TMB-8扩张PA的作用减弱。结论:TMB-8能扩张痉挛的脑血管,可能与其钙拮抗和一氧化氮释放作用有关。     

N-乙酰半胱氨酸和L-NAME对磷化铝诱导的大鼠心血管毒性的作用(英文)

AIM: To investigate the protective effects of N-acetyl-cysteine (NAC) and N~ω-Nitro-L-arginine methyl ester(L-NAME) on aluminium phosphide (AlP) poisoninginduced hemodynamic changes, myocardial oxygen freeradical in injury and on survival time in rats. METH-ODS: AlP (12.5 mg/kg) was administered intragastri-cally under urethane anaesthesia. The effect of pre- andpost-treatment with NAC and L-NAME alone and incombination was studied on haemodynarnic parameters[blood pressure (BP), heart rate (HR), and electrocar-diogram (ECG) ] and biochemical parameters (malonyl-     

链佐星所致糖尿病大鼠主动脉内皮依赖舒张反应损伤的特征(英文)

目的:研究早期糖尿病大鼠内皮依赖舒张反应(EDR)损伤的机制。方法:离体主动脉环张力实验。结果:乙酰胆碱(ACh),组胺(His),缓激肽,环匹阿尼酸(CPA)在糖尿病组EDR均比对照组明显减弱。而卡西霉素诱导的EDR未见损伤。L-NAME(0.3mmol·L~(-1))预处理取消所有EDR,并使两组间效应均一化。ACh或CPA诱导最大EDR时,卡西霉素(1μmol·L~(-1))进一步扩张糖尿病而非正常组血管环。硝普钠扩血管及CPA或His缩血管效应均无组间差异。结论:在4周链佐星糖尿病大鼠主动脉,受体而不是非受体介导的EDR普遍损伤,其机制与内皮细胞电容性钙内流信号通路受损从而使NO合成减少有关。     

保留幽门的转流术治疗肠系膜上动脉综合征临床应用与评价(附12例报道)

目的探讨肠系膜上动脉综合征的有效手术治疗方法。方法采用保留幽门的Roux-en-y胃、十二指肠、空肠上段吻合,使食物转流直接进入空肠,不再通过十二指肠。结果保留幽门的转流术治疗肠系膜上动脉综合征12例,随访6³6个月,平均30个月,术前症状消失,体质量增加,均无手术后的胃排空延迟。胃镜检查显示无吻合口溃疡,幽门功能正常。结论保留幽门的转流术是治疗肠系膜上动脉综合征的有效方法,优于十二指肠空肠吻合术,且手术简单,并发症少。本术式保持了胃和幽门的完整性,保留了胃的消化和储存功能,改善了患者的营养状况,且预防了胆汁反流性胃炎、小胃综合征、倾倒综合征及吻合口溃疡的发生。凡具有手术治疗指征且不伴有胃和十二指肠溃疡患者均可采用此方法。     

多巴胺对小鼠神经母细胞瘤和大鼠神经胶质瘤的杂交(NG108)细胞在体外的毒性(英文)

目的:研究多巴胺(DA)对小鼠神经母细胞瘤和大鼠神经胶质瘤的杂交细胞NG108的毒性.方法:用MTT法测定NG108细胞的活性.结果:当DA浓度在100 μmol L~(-1)时对NG108细胞有毒性作用.这时的细胞活性仅为对照的1/4左右.DA受体拮抗剂舒必利和Sch-23390不能阻断DA毒性,表明DA对NG108细胞的毒性作用不是由DA受体介导的.DA(125 μmol L~(-1))的毒性作用能被过氧化氢酶(50 kU L~(-1))、超氧化物歧化酶(50kU L~(-1))和维生素C(200 μmol L~(-1))抑制.它们分别能使NG108细胞的活性由DA单独作用时的25.9±11.0％上升到74.8±4.4％、72.3±4.5％和71.4±2.3％.结论:DA对NG108细胞的毒性作用是由DA氧化代谢产生的有毒产物如过氧化氢引起的.     

格列本脲和亚甲蓝对缺氧诱发离体猪冠脉—过性舒张的影响

缺氧可诱发KC1 25 mmol·L~(-1)预收缩离体猪冠脉产生双相反应,先短暂(持续4.3±s0.8 min)舒张,随后持续收缩;除去内皮可消除缺氧诱发的冠脉舒张反应,并几乎完全消除收缩反应,格列本脲0.1,0.5,2.5和亚甲蓝5,10μmol·L~(-1)均可浓度依赖地抑制缺氧诱发的冠脉舒张反应;格列本脲2.5和亚甲蓝10μmol·L~(-1)合用可几乎完全消除此种舒张反应,提示缺氧诱发离体猪冠脉一过性舒张可能由ATP敏感性钾通道和内皮舒张因子(EDRF)共同中介。     

Mechanisms underlying impairment of endothelium-dependent relaxation by fetal bovine serum in organ-cultured rat mesenteric artery

Organ culture of blood vessels provides a useful technique to investigate long-term effects of drugs because tissue architecture and function are well preserved. Various growth factors are responsible for structural and functional changes during vascular diseases. We investigated long-term effects of fetal bovine serum (FBS) which contains such factors on endothelium-dependent relaxation using organ-culture method. Rat isolated mesenteric arteries with endothelium were cultured for 3 days without or with 10% FBS (FBS). Acetylcholine- and bradykinin-induced endothelium-dependent relaxations were significantly impaired in FBS, whereas sodium nitroprusside-induced relaxation of endothelium-removed artery was unchanged. Morphological examination revealed that endothelium was intact in FBS. Acetylcholine-induced nitric oxide (NO) release as detected by 4, 5-diaminofluorescein significantly decreased in FBS, whereas endothelial NO synthase expression was unchanged. A Ca²⁺ ionophore, A23187-induced relaxation was unchanged in FBS. A phospholipase C activator, m-3M3FBS-induced relaxation of FBS was unchanged in either Ca²⁺-containing or -free solution. Total expressions of transient receptor potential canonical channels (TRPCs: TRPC-1, -4, -5) were similar in FBS. These data suggest that FBS impairs endothelium-dependent relaxation by inhibiting events upstream of phospholipase C activation including phospholipase C, G-protein, and receptors in endothelium.     

Recovery by ascorbate of impaired nitric oxide-dependent relaxation resulting from oxidant stress in rat aorta

1. In this study we investigated the ability of ascorbate to protect nitric oxide from destruction by superoxide anion.
2. Ascorbate produced concentration-dependent relaxation of rings of rat aorta, comprising two components: the first, seen at 1–300 μM, reached a maximum of 45.3±2.8%, and was abolished by endothelial removal or treatment with L-NAME (100 μM), demonstrating involvement of nitric oxide. The second occurred at concentrations of 1 mM and above and was associated with falls in the pH of the bathing fluid.
3. Pretreatment with ascorbate at concentrations up to 3 mM had no effect on the relaxation to acetylcholine (10 nM–10 μM) on endothelium-containing rings or adenosine (0.1 μM–3 mM) on endothelium-denuded rings.
4. An oxidant stress was applied to aortic rings, comprising inhibition of endogenous Cu/Zn superoxide dismutase by diethyldithiocarbamate (0.1 mM) followed by generation of superoxide anion by hypoxanthine (0.1 mM/xanthine oxidase (16 u ml⁻¹). This reduced maximal acetylcholine-induced relaxation from 96.7±1.3% to 42.4±3.5% (P<0.001). Treatment with ascorbate (30 μM–3 mM) reversed this blockade in a concentration-dependent manner.
5. Our findings show that ascorbate has the ability to protect nitric oxide from destruction by superoxide anion. This action is seen with ascorbate at levels normally present in plasma, suggesting that this antioxidant may exert a tonic protective effect on nitric oxide within the vasculature.

     

Potassium channel activation and relaxation by nicorandil in rat small mesenteric arteries

1. We used whole-cell patch clamp to investigate the currents activated by nicorandil in smooth muscle cells isolated from rat small mesenteric arteries, and studied the relaxant effect of nicorandil using myography.
2. Nicorandil (300 μM) activated currents with near-linear current-voltage relationships and reversal potentials near to the equilibrium potential for K⁺.
3. The nicorandil-activated current was blocked by glibenclamide (10 μM), but unaffected by iberiotoxin (100 nM) and the guanylyl cyclase inhibitor LY 83583 (1 μM). During current activation by nicorandil, openings of channels with a unitary conductance of 31 pS were detected.
4. One hundred μM nicorandil had no effect on currents through Ca²⁺ channels recorded in response to depolarizing voltage steps using 10 mM Ba²⁺ as a charge carrier. A small reduction in current amplitude was seen in 300 μM nicorandil, though this was not statistically significant.
5. In arterial rings contracted with 20 mM K⁺ Krebs solution containing 200 nM BAYK 8644, nicorandil produced a concentration-dependent relaxation with mean pD₂=4.77±0.06. Glibenclamide (10 μM) shifted the curve to the right (pD₂=4.32±0.05), as did 60 mM K⁺. LY 83583 caused a dose-dependent inhibition of the relaxant effect of nicorandil, while LY 83583 and glibenclamide together produced greater inhibition than either alone.
6. Metabolic inhibition with carbonyl cyanide m-chlorophenyl hydrazone (30 nM), or by reduction of extracellular glucose to 0.5 mM, increased the potency of nicorandil.
7. We conclude that nicorandil activates K_ATP channels in these vessels and also acts through guanylyl cyclase to cause vasorelaxation, and that the potency of nicorandil is increased during metabolic inhibition.

     

The vascular effects of different arginase inhibitors in rat isolated aorta and mesenteric arteries

Background and purpose

Arginase and nitric oxide (NO) synthase share the common substrate L-arginine, and arginase inhibition is proposed to increase NO production by increasing intracellular levels of L-arginine. Many different inhibitors are used, and here we have examined the effects of these inhibitors on vascular tissue.

Experimental approach

Each arginase inhibitor was assessed by its effects on isolated rings of aorta and mesenteric arteries from rats by: (i) their ability to preserve the tolerance to repeated applications of the endothelium-dependent agonist acetylcholine (ACh); and (ii) their direct vasorelaxant effect.

Key results

In both vessel types, tolerance (defined as a reduced response upon second application) to ACh was reversed with addition of L-arginine, (S)-(2-boronethyl)-L-cysteine HCl (BEC) or N^G-Hydroxy-L-arginine (L-NOHA). On the other hand, N^ω-hydroxy-nor-L-arginine (nor-NOHA) significantly augmented the response to ACh, an effect that was partially reversed with L-arginine. No effect on tolerance to ACh was observed with L-valine, nor-valine or D,L, α-difluoromethylornithine (DFMO). BEC, L-NOHA and nor-NOHA elicited endothelium-independent vasorelaxation in both endothelium intact and denuded aorta while L-valine, DFMO and nor-valine did not.

Conclusions and implications

BEC and L-NOHA, but not nor-NOHA, L-valine, DFMO or nor-valine, significantly reversed tolerance to ACh possibly conserving L-arginine levels and therefore increasing NO bioavailability. However, both BEC and L-NOHA caused endothelium-independent vasorelaxation in rat aorta, suggesting that these inhibitors have a role beyond arginase inhibition alone. Our data thus questions the interpretation of many studies using these antagonists as specific arginase inhibitors in the vasculature, without verification with other methods.     

Mechanisms for the induction of oxidative stress in Syrian hamster embryo cells by acrylonitrile.

Chronic administration of acrylonitrile to rats resulted in an increase in the incidence of glial neoplasms of the brain. Recent studies have shown that acrylonitrile induces oxidative stress in rat brain and cultured rat glial cells. Acrylonitrile also induces morphological transformation concomitant with an increase in the formation of oxidized DNA in Syrian Hamster Embryo (SHE) cells in a dose-dependent manner. The mechanism for the induction of oxidative stress in SHE cells remains unresolved. The present study examined the effects of acrylonitrile on enzymatic and nonenzymatic antioxidants in SHE cells. SHE cells were treated with subcytolethal doses of acrylonitrile (0, 25, 50, and 75 microg/ml) for 4, 24, and 48 h. Acrylonitrile (50 microg/ml and 75 microg/ml) increased the amount of reactive oxygen species in SHE cells at all time points. Glutathione (GSH) was depleted and catalase and superoxide dismutase activities were significantly decreased in SHE cells after 4 h of treatment. The inhibition of these antioxidants was temporal, returning to control values or higher after 24 and 48 h. Xanthine oxidase activity was increased following 24 and 48 h treatment with acrylonitrile. 1-aminobenzotriazole, a suicidal P450 enzyme inhibitor, attenuated the effects of acrylonitrile on catalase and xanthine oxidase in SHE cells, suggesting that P450 metabolism is required for acrylonitrile to produce its effects on these enzymes. Additional studies showed that in the absence of metabolic sources acrylonitrile had no effect on either catalase or superoxide dismutase activity. These results suggest that the induction of oxidative stress by acrylonitrile involves a temporal decrease in antioxidants and increase in xanthine oxidase activity that is mediated by oxidative metabolism of acrylonitrile.     

Impairment of both nitric oxide-mediated and EDHF-type relaxation in small mesenteric arteries from rats with streptozotocin-induced diabetes

BACKGROUND AND PURPOSE

To investigate whether diabetes affects either or both nitric oxide (NO)-mediated and endothelium-derived hyperpolarizing factor (EDHF)-type relaxation in endothelium-dependent relaxation of mesenteric arteries from streptozotocin-induced diabetic rats.

EXPERIMENTAL APPROACH

Wire myography was employed to examine endothelial function of mesenteric arteries. Superoxide levels were measured by L-012 and lucigenin-enhanced chemiluminescence. Western blotting was used to quantify protein expression levels.

KEY RESULTS

Superoxide levels were significantly increased in diabetic mesenteric arteries compared with normal arteries. Diabetes significantly reduced the sensitivity to the endothelium-dependent relaxant, acetylcholine (ACh) in mesenteric arteries. When the contribution of NO to relaxation was abolished by N-nitro-L-arginine (L-NNA) + a soluble guanylate cyclase inhibitor (ODQ), the sensitivity to ACh was significantly decreased in the diabetic arteries compared with normal arteries, indicating an impaired EDHF-type relaxation despite increased expression of intermediate- and small-conductance calcium-activated potassium channels. Conversely, when the contribution of EDHF was inhibited with TRAM-34 + apamin + iberiotoxin, maximum relaxations to ACh were significantly decreased in diabetic compared with normal arteries, suggesting that the contribution of NO was also impaired by diabetes. Basal levels of NO release, indicated by contraction to L-NNA, were also significantly decreased in diabetic arteries. Western blot analysis demonstrated that diabetic arteries had an increased expression of Nox2, decreased pSer⁴⁷³Akt and a reduced proportion of endothelial NO synthase (eNOS) expressed as a dimer, indicating uncoupling.

CONCLUSION AND IMPLICATIONS

The contribution of both NO and EDHF-type relaxations was impaired in diabetes and was caused by increased oxidative stress, decreased pSer⁴⁷³Akt and/or eNOS uncoupling.     

Potentiation by vasopressin of adrenergic vasoconstriction in the rat isolated mesenteric artery

1. The aim of the present study was to investigate in rat mesenteric artery rings whether low concentrations of vasopressin could modify the contractile responses to noradrenaline and electrical stimulation of perivascular nerves.
2. Vasopressin (10⁻¹⁰–10⁻⁷ M) caused concentration-dependent contractions (pD₂=8.36±0.09). The V₁-receptor antagonist d(CH₂)₅Tyr(Me)AVP (10⁻⁹–10⁻⁸ M) produced parallel rightward shifts of the control curve for vasopressin. Schild analysis yielded a pA₂ value of 9.83 with a slope of 1.10±0.14.
3. Vasopressin (3×10 ⁻¹⁰ and 10⁻⁹ M) caused concentration-dependent potentiation of the contractions elicited by electrical stimulation (2–8 Hz; 0.2 ms duration for 30 s) and produced leftward shifts of the concentration-response curve for noradrenaline. The V₁-receptor antagonist induced concentration-dependent inhibitions of potentiation induced by vasopressin. The selective V₁-receptor agonist [Phe^*, Orn⁸]-vasotocin (3×10 ⁻¹⁰ and 10⁻⁹ M) induced potentiation of electrical stimulation-evoked responses which was also inhibited in the presence of the V₁ antagonist (10⁻⁸ M). In contrast, the V₂-receptor agonist deamino-8-D-arginine vasopressin (desmopressin 10⁻⁸–10⁻⁷ M) did not modify the electrical stimulation-induced responses and the V₂-receptor antagonist [d(CH₂)₅, D-Ile^*, Ile⁴, Arg⁸]-vasopressin (10⁻⁸–10⁻⁷ M) did not affect the potentiation evoked by vasopressin.
4. In artery rings contracted by 10⁻⁶ M noradrenaline in the presence of 10⁻⁶ M guanethidine and 10⁻⁶ M atropine, electrical stimulation (2, 4 and 8 Hz) produced frequency-dependent relaxations which were unaffected by 10⁻⁹ M vasopressin but abolished by 10⁻⁶ M tetrodotoxin.
5. Vasopressin also potentiated contractions elicited by KCl and contractions induced by addition of CaCl₂ to KCl depolarized vessels. The augmenting effects were inhibited by the V₁ antagonist.
6. In the presence of the calcium antagonist nifedipine (10⁻⁶ M), vasopressin failed to enhance the contractile responses to electrical stimulation, noradrenaline and KCl.
7. The results demonstrate that low concentrations of vasopressin strongly potentiate the contractions to adrenergic stimulation and KCl depolarization. This effect appears to be mediated by V₁ receptor stimulation which brings about an increase in calcium entry through dihydropyridine-sensitive calcium channels.

     

Effects of the antihypertensive agent,cicletanine, on noradrenaline release and vasoconstriction in perfused mesenteric artery of SHR

1. The mechanism by which cicletanine (CIC) exerts its antihypertensive effects has not been fully elucidated. The present study was undertaken to examine the effects of in vivo and in vitro treatment with CIC on the pressor response and noradrenaline (NA) overflow during periarterial nerve stimulation (PNS) in perfused mesenteric arterial beds isolated from spontaneously hypertensive rats (SHR).
2. CIC at a dose of 50 mg kg⁻¹ day⁻¹ was administered orally to both SHR and normotensive Wistar-Kyoto rats (WKY) from the 6th to 10th week of age. At the 10th week, the isolated mesenteric arterial bed was perfused with Krebs-Henseleit buffer and changes in perfusion pressure and NA overflow during PNS were measured.
3. Chronic treatment with CIC suppressed the age-related elevation of systemic blood pressure in SHR but not in WKY.
4. The PNS (20 Hz)-induced mesenteric vasoconstrictor response and NA overflow were greater in SHR than in WKY. In the vasculature of SHR chronic treatment with CIC resulted in a significant attenuation of the vasoconstriction and the NA overflow during PNS, whereas it did not alter vasoconstrictor responses to bolus injections of KCl and phenylephrine.
5. Treatment with 30 μM CIC in vitro diminished the PNS-induced vasoconstriction and NA overflow but not the NA- and KCl-induced vasoconstriction in the vasculature of untreated SHR.
6. In the vasculature of SHR PNS-induced NA overflow was attenuated by prostaglandin E₂ (0.05 μM), whereas it was augmented by the cyclo-oxygenase inhibitor diclofenac-Na (30 μM). In the presence of diclofenac, in vitro treatment with CIC did not attenuate the NA overflow during PNS.
7. The results suggest that the antihypertensive effect of CIC in SHR is partially due to the presynaptic inhibition of NA release during sympathetic nerve activation. Transjunctional inhibition of NA release by prostaglandins may contribute to the inhibitory action of CIC on NA release in the vasculature of SHR.