血管内皮舒张因子的作用及其对疾病发生发展的影响

自从1980年Furchgott等发现内皮依赖性舒张作用以来,血管内皮就被认为是调节血管平滑肌张力的重要功能单位.血管内皮细胞可通过释放前列环素(PGI_2)、内皮舒张因子(EDRF)、内皮超极化因子(EDHF)、内皮收缩因子(EDCF)等血管活性物质来调节血管平滑肌张力.其中,血管内皮舒张因子具有舒张血管平滑肌和抑制血小板活性的作用,它能介导许多内源性血管活性物质的舒张     

内皮衍生松弛因子和收缩因子：新概念和新发现

血管内皮细胞是松弛因子和收缩因子的来源,这些有待进一步确定的物质称为内皮细胞衍生松弛因子(EDRF)和内皮细胞衍生收缩因子(EDCF)。EDRF是血管松弛反应的重要介质,除了其舒血管作用外,最近发现EDRF尚能抑制血小板聚集,它不仅可调整缩血管药物升高血压的能力,且能调节平滑肌张力水平。由于EDRF的半衰期很短(约6秒),有关调节EDRF的合成、释放和作用的因素所知甚少。EDRF的最后鉴定和结构改造必将产生一些对心力衰竭、高血压、动脉粥样硬化、心绞痛以及外周和脑血管疾病可     

高血压病、血管内皮和心血管危险因子

血管内皮在调节血管的渗透选择性,控制止血功能和影响血液细胞成分与非细胞成分问的相互作用方面起着决定性的作用。内皮所释放的扩血管物质有PGI_2(前列环素),血管活性物质有儿茶酚胺类、缓激肽、5-HT和血管紧张素Ⅱ,内皮通过这些物质而调节血管的张力。Furchgott等1980年报告,乙酰胆碱对离体动脉血管平滑肌的松弛作用必须依赖功能完整的血管内皮,他们还将其所释放的因子命名为EDRF(内皮衍生的血管舒张因子)。许多促效剂和机械刺激都能使各种血管床包括肾小球释放EDRF。现已知道,EDRF(至少最重要的EDRF)是一氧化氮(NO),由     

一氧化氮,内皮素与原发性高血压的关系

原发性高血压是危害人类健康的常见病、多发病,有关其发病机制比较复杂。近年细胞生物学及分子生物学的研究表明,血管内皮不仅在血管平滑肌和循环血液之间形成一层生理屏障,摄取、代谢血液中的血管活性物质,尤其能合成和释放多种血管活性物质,内皮衍生舒张因子(EDRF,endothelium derived relaxing factor)和内皮衍生收缩因子(EDCF,endothclium derived contracting factor)就是其中两种。EDRF的最终效应分子一氧化氮     

ZW1-2对局灶脑缺血小鼠纹状体、皮质及海马脑区BDNF和VEGF蛋白表达的影响

目的观察化合物zome wermel 1-2(ZW1-2)对小鼠永久性局灶脑缺血后的神经功能,以及对脑源性营养因子和血管内皮生长因子的影响。方法制备小鼠永久性局灶脑缺血模型,并分别于脑缺血后2.5 h和7.5 h,灌胃给予不同剂量的化合物ZW1-2,脑缺血后24 h采用免疫组化法测定小鼠各个脑缺血易损区的脑源性神经营养因子和血管内皮生长因子表达情况。结果 ZW1-2能够显著降低小鼠局灶性脑缺血导致的行为功能评分,可以显著提高皮质、纹状体和海马脑区的脑源性神经营养因子表达,显著降低这些脑区中的血管内皮生长因子蛋白表达。结论 ZW1-2具有抗实验性脑缺血作用,其作用机制可能通过调控脑源性神经营养因子以及血管内皮生长因子而起到对脑缺血损伤的治疗作用。     

小檗碱联合他汀类药物治疗高脂血症的临床疗效和安全性研究与分析

动脉粥样硬化是心血管疾病(CVD)的主要发病因素[1]。动脉粥样硬化的风险因素,例如高胆固醇血症、糖尿病和动脉高血压均与内皮功能障碍有关。内皮功能障碍是CVD的早期病理学变化,导致斑块的发生发展[2]。内皮功能障碍会促炎症和促血栓形成,在动脉粥样硬化的发生发展中发挥了关键的作用。内皮细胞暴露于高胆固醇血症的关键事件为内皮细胞源性血管舒张因子(EDRF)释放减少[3],而降低胆固醇水平似乎有利于改善内皮细胞功能[4]。     

内皮素与创伤性脑水肿的相关性研究进展

近年来对创伤性脑水肿的病理生理学从不同侧面进行了研究，涉及到血脑屏障、钙离子通道、氧自由基等，其中神经体液因素，尤其是调节血管收缩舒张的血管内源性因子的研究更是引人注目。血管内皮细胞(VEC)可以产生释放内皮舒张因子(EDRF)、内皮收缩因子(EDCF)，其中内皮素(endothelins，ET)无论是在体内还是体外试验中，均显示出高效而持久的缩血管效应。     

神经肽Y对离体兔脑血管的作用及其内皮依赖关系

神经肽Y对离体兔脑基底动脉的作用表现在:(1)直接收缩;(2)增强组胺的收缩效应;(3)抑制乙酰胆碱和腺苷的舒张效应。作用(1)和(3)不依赖于血管内皮的存在,而作用(2)依赖血管内皮,其机理可能是由于神经肽Y对血管内皮舒张因子(EDRF)的释放或作用具有抑制性影响。     

自由基使血管舒张因子从主动脉内皮细胞与平滑肌细胞中释放(英文)

电解Krebs液产生自由基,灌流通过有内皮细胞或去内皮细胞的家兔主动脉;或通过生长在微粒上的小牛主动脉内皮细胞柱;用淋浴生物检定法均检测出由血管内皮细胞或血管平滑肌释放出的血管舒张因子。这种血管舒张因子与用ADP通过血管内皮细胞柱释放的血管内皮舒张因子(EDRF)有类似的性质,即作用时间短暂,并可被同时灌注N-硝基-L-精氨酸(为EDRF合成拮抗剂)或血红蛋白(为EDRF清除剂)所减弱。在去内皮细胞的主动脉,ADP的释放作用消失,但自由基的释放作用仍存在,表明血管平滑肌也可释放,因羟自由基消除剂水杨酸钠能明显减弱电解产生的自由基的这种释放作用,故推测电解产生的羟自由基在释放血管舒张因子中起主要作用。     

eNOS磷酸化与酶活性及中药介入

作为内皮源性血管舒张因子,内皮源性一氧化氮合酶(endothelial nitric oxide synthase,eNOS)衍生的一氧化氮(nitric oxide,NO)在维持血管稳态和预防血管病变中起着至关重要的作用。eNOS的活性调控涉及复杂而精密的信号通路及分子机制,尤其是多个不同位点的氨基酸残基的磷酸化在其活性调控中发挥关键作用。该文就其主要的氨基酸残基的磷酸化对eNOS酶活性的影响及相关的信号通路,以及中药对其干预的研究现状做一综述。     

Responses to endothelium-derived factors and their interaction in mesenteric arteries from Wistar-Kyoto and stroke-prone spontaneously hypertensive rats

1. Responses to endothelium-derived nitric oxide (EDNO), indomethacin-sensitive endothelium-derived contracting factor (EDCF) and hyperpolarization by endothelium-derived hyperpolarizing factor (EDHF) and the interaction among these factors in mesenteric arteries from 16-week-old Wistar Kyoto (WKY) rats and age-matched stroke-prone spontaneously hypertensive rats (SHRSP) were studied, observing the time-course of the response to 10-5 mol/L acetylcholine (ACh). 2. The effects of EDNO, EDCF and EDHF were blocked by Nomega-nitro-l-arginine (10-4 mol/L), indomethacin (10-5 mol/L) and a combination of apamin (5 x 10-6 mol/L) and charybdotoxin (10-7 mol/L), respectively. 3. The response to EDNO observed in the absence of EDCF and EDHF was not different between preparations from WKY rats and SHRSP. The response to EDCF observed in the absence of EDNO and EDHF was slightly greater in preparations from SHRSP. The response to EDHF in the absence of EDNO and EDCF was much greater in preparations from WKY rats. 4. Endothelium-derived contracting factor attenuated the relaxation in response to EDNO, the attenuation being greater in preparations from SHRSP. Relaxation in response to EDNO was blocked by EDHF in preparations from WKY rats, but not in preparations from SHRSP. 5. The response to EDCF was augmented by both EDNO and EDHF. The augmentation was greater in preparations from SHRSP. 6. The response to EDHF was attenuated by EDNO in preparations from WKY rats, but not in preparations from SHRSP. The response to EDHF was attenuated by EDCF in preparations from both WKY rats and SHRSP, the attenuation being greater in preparations from SHRSP. 7. These results suggest that there are interactions among these factors in terms of their release or the response to ACh in mesenteric arteries that differ between preparations from WKY rats and SHRSP. In addition, involvement of factors other than these three factors, which also differs between preparations from WKY rats and SHRSP, is suggested.     

ENDOTHELIAL DYSFUNCTION EXACERBATES THE IMPAIRMENT OF RELAXATION BY LYSOPHOSPHATIDYLCHOLINE IN PORCINE CORONARY ARTERY

1. Current evidence suggests that lysophosphatidylcholine (LPC), a component found in oxidized low-density lipoprotein (Ox-LDL), inhibits endothelium-dependent relaxation (EDR) mediated by endothelium-derived relaxing factor (EDRF) and endothelium-derived hyperpolarizing factor (EDHF). An objective of the present study was to characterize the roles of the different elements of EDR in LPC-induced impairment within the porcine coronary artery. Concomitantly, we sought to determine whether impairment of one component of EDR would increase the sensitivity of the endothelium to LPC. 2. Bradykini. (0.1 nmol/L-0.3 μmol/L) relaxed U46619 (30 nmol/L)-precontracted porcine coronary artery rings in a concentration-dependent manner. A reduction in the bradykinin-elicited response was observed in N^G-nitro-L-arginine methyl ester (L-NAME; 300 μmol/L)- and ouabain (50 μmol/L)-treated rings. Pretreatment with LPC (20 μmol/L), which on its own had no effect on normal endothelial relaxation, resulted in further inhibition of EDRF- and EDHF-induced relaxations. 3. Our results demonstrate that EDRF and EDHF are the primary mediators of EDR in the porcine coronary artery. Our data also show that while a low concentration of LPC (20 μmol/L) does not impair EDR, it can evoke vascular dysfunction following blockade of either the effects of EDRF or EDHF. Therefore, these data suggest that the partially damaged vascular endothelium could be more sensitive to threshold levels of this atherogenic phospholipid.     

ENDOTHELIUM-DERIVED RELAXING FACTOR RELEASED FROM CULTURED CELLS: DIFFERENTIATION FROM NITRIC OXIDE

1. Endothelium-derived relaxing factor (EDRF) is an extremely labile mediator thought to be identical to nitric oxide (NO). 2. A cascade superfusion technique was used to bioassay EDRF released from bovine aortic endothelial cells grown to confluence on microcarrier beads. 3. Bradykinin (1-100 nmol/l), infused through a 1 cm column of endothelial cells on microcarriers, released an EDRF-like substance that caused relaxations of de-endothelialized strips of rabbit aorta (precontracted with phenylephrine). These relaxations diminished on successive tissues in the cascade, when compared with those produced by glyceryl trinitrate as a stable standard. 4. Haemoglobin (1 mumol/l), infused directly over the bioassay tissues, abolished bradykinin-induced relaxations and these were restored within 5 min after removal of haemoglobin. The infusion did not affect the relaxations produced by glyceryl trinitrate in this system. 5. Methylene blue (20 mumol/l) inhibited bradykinin-induced relaxations when infused over the rabbit aortae, and reduced those relaxations produced by glyceryl trinitrate. The effects of bradykinin, but not glyceryl trinitrate, were partially restored after removing methylene blue. 6. These data are consistent with the known effects of these compounds on the activity of NO, and on EDRF in isolated blood vessels. 7. The activity of EDRF (released by bradykinin) was compared directly with NO on strips of guinea-pig trachea (de-epithelialized) interposed in cascade between two rabbit aortae; all strips were precontracted with histamine and phenylephrine. 8. A submaximal dose of NO that matched the relaxation produced by EDRF on the uppermost aorta, caused relaxation of the trachea, but EDRF had no effect on this tissue. In addition, the NO-induced relaxation of the lower aorta was greater than that produced by EDRF. 9. These data indicate that EDRF does not have identical biological activity to NO. EDRF could contain an NO moiety attached to a carrier molecule that is bound and stabilized in tracheal tissue.     

l-ARGININE INFUSION INDUCES HYPOTENSION AND DIURESIS/NATRIURESIS WITH CONCOMITANT INCREASED URINARY EXCRETION OF NITRITE/NITRATE AND CYCLIC GMP IN HUMANS

1. The vascular endothelium produces endothelium-derived relaxing factor (EDRF) or nitric oxide (NO), which exerts vasodilation through cyclic guanosine monophosphate (cGMP) as a second messenger. To determine whether EDRF has any vasodilating and natriuretic action in man, the present study examined the effects of L-arginine (L-Arg), a substrate for NO, on the responses of mean blood pressure (MBP) and heart rate (HR); plasma concentrations of cGMP, atrial natriuretic factor (ANF) and nitrite/nitrate (NOx); urinary excretion of sodium, cGMP and NOx; and urinary flow in eight normal male subjects. These parameters were compared with those following saline infusion in the same subjects. Clearance of para-aminohippuric acid (PAH) and inulin was studied in five normal subjects. 2. Infusion of L-Arg (30 g) caused a significant fall in MBP (-8 mmHg) with a concomitant rise in HR (10 beats/min), while saline infusion had no effects on these parameters. 3. Neither L-Arg nor saline infusion caused appreciable changes in plasma concentrations of ANF or NOx. Plasma cGMP concentrations increased significantly during (1.7-fold) and after (1.9-fold) L-Arg infusion, but only slightly (1.3-fold) during saline infusion. 4. Urine flow increased more remarkably following L-Arg infusion than that following saline infusion. Remarkable increases in urinary excretion of sodium and fractional excretion of sodium were observed after L-Arg infusion compared with those after saline infusion. Natriuresis was associated with enhanced urinary excretion of cGMP and Nox. Urinary Nox excretion showed positive correlations with urinary flow (r = 0.69, P less than 0.001) and with urinary cGMP excretion (r = 0.60, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Endothelium-dependent contractile actions of proteinase-activated receptor-2-activating peptides in human umbilical vein: release of a contracting factor via a novel receptor

1. The contractile actions of the proteinase-activated receptor-2-activating peptides (PAR₂APs), SLIGRL-NH₂ (SL-NH₂), SLIGKV-NH₂ (KV-NH₂), trans-cinnamoyl-LIGRLO-NH₂ (tc-NH₂), and the PAR₁-AP, TFLLR-NH₂ (TF-NH₂) as well as trypsin and thrombin were studied in endothelium-denuded and intact human umbilical vein (HUV) ring preparations.
2. In HUV rings with, but not without an intact endothelium, PAR₂APs caused a concentration-dependent contractile response, whereas LSIGRL-NH₂ trypsin and PAR₁APs were inactive. The contractile response was not affected by the endothelin ET_A receptor antagonist, BQ123, the cyclooxygenase inhibitor, indomethacin, the leukotriene synthesis inhibitor, MK886, or the epoxygenase/P450 inhibitor, SKF-525A. Other pharmacological antagonists (prazosin, Losartan®) were similarly inactive.
3. The order of potencies of the PAR₂APs to cause a contraction in the endothelium-intact preparation was: SL-NH₂>>KV-NH₂⩾tc-NH₂.
4. Using an endothelium-free rat aorta ring as a reporter tissue, surrounded with endothelium-intact HUV as a donor tissue in a `sandwich assay,'' we also monitored the ability of SL-NH₂, TF-NH₂, trypsin and thrombin to release either contractile (EDCF) or relaxant (EDRF) factors.
5. In the `sandwich assay'' done in the presence of L-NAME (0.1 mM), the endothelium-intact HUV tissue (but not endothelium-denuded HUV) released a contractile factor (EDCF) in response to SL-NH₂ (50 μM) but not to trypsin or LSIGRL-NH₂. The SL-NH₂-mediated release/action of the EDCF was not affected by BQ123, indomethacin, MK886 or SKF-525A.
6. In the `sandwich assay'', trypsin (4–10 nM), SL-NH₂, KV-NH₂ and tc-NH₂ caused the release of a relaxant activity (EDRF) from the endothelium-intact (but not the denuded) HUV preparation. The release of EDRF was blocked by 0.1 mM ^ωnitro-L-arginine-methylester (L-NAME). Neither thrombin (10 u ml⁻¹, 100 nM) nor TF-NH₂ (50 μM) were active in this EDRF-release assay.
7. The relative potencies of the PAR₂ agonists for causing the release of EDRF in the HUV sandwich assay were: trypsin>>SL-NH₂>>tc-NH₂>KV-NH₂. This order of potencies differed from the one observed for the same agonists in the HUV contraction assay (above) and in an intracellular calcium signalling assay, conducted with cloned human PAR₂ that was expressed in cultured rat kidney KNRK cells: trypsin>>SL-NH₂=tc-NH₂>KV-NH₂.
8. We conclude that PAR₂APs (but not PAR₁APs) via a receptor distinct from PAR₂, can cause a contractile response in endothelium-intact HUV tissue via the release of a diffusable EDCF, that is different from previously recognized smooth muscle agonists (e.g. prostanoid metabolites, endothelin, noradrenaline, angiotensin-II, acetylcholine).

     

Endothelium removal augments endothelium-independent vasodilatation in rat mesenteric vascular bed

BACKGROUND AND PURPOSE: The vascular endothelium regulates vascular tone by releasing various endothelium-derived vasoactive substances to counteract excess vascular response. We investigated whether the vascular endothelium regulates vasodilatation via released endothelium-derived contracting factors (EDCFs), by examining the effect of endothelium removal on responses to periarterial nerve stimulation (PNS) and various vasodilator agents. EXPERIMENTAL APPROACH: The rat mesenteric vascular bed was perfused with Krebs solution. Vasodilator responses to PNS and 5 min perfusion of vasodilator agents in preparations with endothelium were compared with those in the same preparations without endothelium. The endothelium was removed by 30 s perfusion with sodium deoxycholate. KEY RESULTS: Endothelium removal significantly augmented vasodilator responses to PNS and calcitonin gene-related peptide (CGRP), isoprenaline (beta-adrenoceptor agonist), SNP and 8-bromo-cGMP (8-Br-cGMP; cGMP analogue) but not BAY41-2272 (soluble guanylate cyclase activator). The augmentation of SNP-induced vasodilatation after denudation was much greater than that of CGRP- or isoprenaline-induced vasodilatation. In the preparations with an intact endothelium, L-NAME (nitric oxide synthase inhibitor) significantly augmented vasodilator responses to PNS and CGRP, isoprenaline, SNP and 8-Br-cGMP, but not BAY41-2272. Indomethacin (cyclooxygenase inhibitor) and seratrodast (thromboxane A(2) receptor antagonist), but not phosphoramidon (endothelin-1-converting enzyme inhibitor) or BQ-123 (selective endothelin type A receptor antagonists), significantly augmented vasodilator responses to PNS and CGRP, isoprenaline, SNP and BAY41-2272. CONCLUSION AND IMPLICATION: These results suggest that the endothelium in rat mesenteric arteries regulates and maintains vascular tone via counteracting not only vasoconstriction through releasing endothelium-derived relaxing factors, but also vasodilatation, in part by releasing an EDCF, thromboxane A(2).     

MECHANISMS OF IMPAIRMENT OF ENDOTHELIUM-DEPENDENT RELAXATION TO ACETYLCHOLINE IN WATANABE HERITABLE HYPERLIPIDAEMIC RABBIT AORTAS

1. The mechanism of impairment of the endothelium-dependent relaxation in response to acetylcholine (ACh) in aortas from Watanabe heritable hyperlipidaemic (WHHL) rabbits was investigated using a modified sandwich (layered) technique. Intact aortas from WHHL rabbits or Japanese white (JW) rabbits as the control were used as donor strips of endothelium-derived relaxing factor (EDFU?) and endothelium-denuded aortas from JW rabbits were used as detector strips. The EDRF released from a donor strip could be directly detected as the relaxation response in a detector strip. 2. The endothelium-dependent relaxations in all rabbit arteries were almost abolished by treatment with N^G-nitro-l-arginine methyl ester (an inhibitor of nitric oxide synthase). 3. The ACh-induced endothelium-dependent relaxations in the donor strips were impaired in WHHL rabbits in comparison with relaxations in JW and heterozygous WHHL rabbits. Similarly, the relaxation in the detector strips induced by EDRF released from donor strips was reduced in WHHL rabbits. There was a good negative correlation between the aortic total cholesterol content in the donor strips and the degree of relaxation in the detector strips from WHHL rabbits. 4. The reduced relaxation in the detector strips when using donor strips with high cholesterol accumulation or atheromatous plaque was not affected by superoxide dismutase plus catalase (scavengers of superoxide anions), indomethacin (an inhibitor of cyclo-oxygenase), ONO-3708 (an antagonist of endoperoxide/ thromboxane receptor) and 97–139 (an antagonist of endothelin ET_A receptor). 5. These results suggest that the mechanism of impaired endothelium-dependent relaxations in atherosclerotic WHHL rabbit aortas may be due to the reduced amount of EDRF, probably nitric oxide, from the endothelium and not due to its inactivation by oxygen-derived free radicals or masking by increased production of endothelium-derived contracting factors.     

氧张力变化对离体兔主动脉内皮细胞释放物质的释放模式和状态的作用(英文)

AIM: To Observe the effect of change in oxygen tensionon the release pattern and nature of endothelium-derivedsubstances in isolated rabbit aorta. METHODS: Iso-metric contractions and relaxations in isolated rabbit stripwere observed in response to changes in oxygen tensionand effect of various drugs was noted on them. RE-SULTS: Change in oxygen tension from high [po_2=(618.9±0.4) mmHg; 1 mmHg= 133.3 Pa] to low[Po_2= (117.6± 0.6) mmHg] was observed to convert     

Endothelium-derived factors in hypertensive blood vessels,especially nitric oxide and hypertension

Endothelium-dependent relaxation (EDR) in the blood vessels of spontaneously hypertensive rats (SHR) and the role of nitric oxide (NO) in the initiation of hypertension are reviewed. EDR was impaired in blood vessels of SHR depending on age and degree of hypertension when compared with those of normotensive rats. The cause of the impairment varied among the type of blood vessels: a decrease in the production of NO and endothelium-derived relaxing factor (EDRF) and an increase in the production of endothelium-derived contracting factor (EDCF) are the main causes of the impairment in large arteries, while a decrease in endothelium-dependent hyperpolarization and increased release of EDCF are the main causes of the impairment in small arteries. Interactions among these endothelium-derived factors and changes in the interactions are also causes of impairment. Superoxide may be involved in the impairment of EDR by destroying NO. The endothelium depresses smooth muscle contraction, including spontaneous tone developed in vascular smooth muscle, and the depressing effect of the endothelium is impaired in the preparations from SHR. The endothelium of blood vessels of SHR are structurally injured as demonstrated by scanning electron microscopy. Antihypertensive treatment prevented these functional and structural changes. Chronic treatment with inhibitors of NO production in normotensive rats impaired EDR and elevated blood pressure. The impairment of EDR is a secondary change due to continued hypertension, and early initiation of antihypertensive therapy is recommended.     

Activation of vascular smooth muscle K+ channels by endothelium-derived relaxing factors

1. Endothelium-derived relaxing factors (EDRF), including nitric oxide (NO), prostacyclin (PGI2) and an as yet uncharacterized endothelium-derived hyperpolarizing factor (EDHF), are now recognized to induce relaxation of vascular smooth muscle, in part via the activation of K+ channels. 2. Experiments using selective K+ channel blockers, including iberiotoxin (IbTX), glibenclamide, apamin and 4-aminopyridine (4-AP) to inhibit endothelium-induced relaxation suggest that more than one type of K+ channel may be involved, depending on the species and tissue, including: (i) large conductance Ca(2+)-activated (BKCa) channels; (ii) ATP-sensitive (KATP) channels; (iii) small conductance Ca(2+)-activated (SKCa) channels; and (iv) voltage-gated (Kv) K+ channels. 3. Recent observations suggest a role for Kv channels in some vessels based on a sensitivity of NO- and PGI2-mediated relaxations to 4-AP, as well as a complete suppression of EDHF-dependent relaxation by a combination of charybdotoxin (ChTX) and apamin but not IbTX and apamin. 4. The molecular identity of the K+ channels affected by EDRF is not well characterized. Recently, findings indicate that the pore-forming alpha-subunit tetramers of vascular smooth muscle BKCa channels are due to the expression of the so-called Slo channel gene. The identities of the KATP, SKCa and Kv channels involved in endothelium-dependent vasodilation are not known. 5. The component of whole-cell Kv current affected by PGI2 may be due to slowly inactivating, 4-AP-sensitive, 15 pS delayed-rectifier K+ channels (KDR); the activity of these channels in vascular myocytes is increased by forskolin and protein kinase A (PKA) and rabbit portal vein Kv1.5 pore-forming alpha-subunits, which appear to be a component of native KDR current and possess consensus phosphorylation sequences for PKA.