实验性糖尿病大鼠阴茎海绵体组织自由基代谢的研究

目的：通过体内实验，探讨试验性糖尿病大鼠阴茎海绵体组织自由基变化。方法：采用黄嘌呤氧化法测定超氧化物岐化酶（SOD）活性，用改良巴比妥酸微量法测定丙二醛（MDA）含量。结果：糖尿病大鼠阴茎海绵体组织SOD明显低于对照组（P＜0．01），MDA明显升高（P＜0．001）。结论：在本实验条件下，实验性糖尿病大鼠阴茎海绵体组织自由基代谢明显障碍，这种变化可能在糖尿病患者阳痿的发生发展中起一定作用。     

固脱汤对失血性休克大鼠血浆NO、6—keto—PGF1α和TXB2含量的影响

目的和方法：观察固脱汤对失血性休克大鼠血浆NO、6－keto-PGF1α和TXA2含量的影响。结果：失血性休克大鼠血浆NO水平增高（P＜0．01），6－keto－PGF1α含量明显降低（P＜0．01），TXA2含量增高（P＜0．01），固脱汤加可明显升高血浆NO、6－keto-PGF1α水平（P＜0．01），而血浆TXB2含量未见显著性改变（P＞0．05）。结论：固脱汤可通过促进血管内皮细胞产生和释放NO及PGI1发挥抗休克作用。     

川芎嗪对妊娠高血压综合征患者血浆TXA2／PGI2平衡的调节和肾功能的影响

目的探讨川芎嗪对妊娠高血压综合征患者血浆TXA2／PGI2平衡的调节和肾功能的影响。方法选择40例轻中度PIH患者．予以川芎嗪120mg静滴10d（川芎嗪治疗组）,另取正常妊娠对照组30例。采用放射免疫法测定血浆TXA2和PGI2的稳定代谢产物TXB2和6-keto-PGF1a浓度。而正常妊娠对照组只测定1次。结果川芎嗪治疗组治疗前与正常妊娠对照组相比较,血浆TXA2含量上升,血浆PGI2含量下降（均P〈0．05）。经过川芎嗪治疗10天后,患者血浆TXA2含量下降。血浆PGI2含量上升（均P〈0．05）;川芎嗪治疗组治疗前与正常妊娠对照组相比较。尿U-MALB和β2-MG均显著升高（P〈0．01）．经过川芎嗪治疗10天后,尿U—MALB和β2-MG明显降低（P〈0．05）。结论川芎嗪具有降低PIH患者血浆TXA2含量和升高PGI2含量,纠正TXA2／PGI2失衡作用,同时川芎嗪还具有提高PIH患者肾小球滤过率和增加肾小管重吸收功能。降低尿蛋白排泄量。保护肾功能作用。     

小麦胚芽油抗动脉粥样硬化的药效学研究

目的：观察小麦胚芽油（wheat germ oil,WGO）对动脉粥样硬化（atherosclerosis,AS）大鼠的治疗效果,并探讨其抗 AS 的可能作用机制。方法连续高脂乳剂灌胃4周,制作 AS 大鼠模型,分别给予各组大鼠连续灌胃不同剂量 WGO 8周;HE 染色光镜下观察大鼠主动脉弓病理形态的改变;酶联免疫吸附试验（ELISA）法检测各组大鼠血清中前列环素（Prostacyclin 2, PGI2）、血栓素 A2（Thromboxane 2,TXA2）及内皮素-1（Endothelin-1,ET-1）的含量。结果2．0 g·kg －1的 WGO 能明显改善 AS大鼠主动脉弓的病理状态,基本恢复正常状态;与模型组比较,1．0、2．0 g·kg －1 WGO 均可显著提高 AS 大鼠血清中 PGI2含量,明显降低 TXA2、ET-1水平（P ＜0．05）。结论WGO 能明显改善 AS 大鼠的动脉粥样硬化状态。其作用机制可能为小麦胚芽油具有良好的调节 PGI2、TXA2平衡,抑制血栓形成,修复内皮损伤以及较强的抗氧化作用。     

阳萎病人阴茎海绵体内血浆中VIP含量的研究

本文对正常人，器质性和精神性阳萎病人进行了研究，在阴茎勃起前后；测定阴茎海绵体内血浆中VIP浓度。对各组受检者行海绵体内注射生理盐水；盐酸罂粟碱，盐酸罂粟碱和酚妥拉明混合液体，每次注射药物间隔时间达30min以上，于海绵体内注射药物前后抽取海绵体内血液，测定血浆中VIP的含量。正常人及各类阳萎病人，在阴茎海绵沐内注射血管活性药物后，所有阴茎发生了勃起，在阴茎勃起过程中，海绵体内血浆中VIP浓度显著升高（P＜0．01）。同时，周围静脉内注射罂粟碱和酚妥拉明混合液体的受检者，在静脉注射药物后；周围静脉血浆中VIP浓度没有显著性变化（P＜0．05）。本实验证实，VIP是参与人类阴茎勃起反应的重要神经递质。     

水蛭醇提物与水提物对肺缺血再灌注模型大鼠的保护作用

目的：研究水蛭醇提物与水提物对肺缺血再灌注模型大鼠的保护作用,并比较两者的作用效果。方法：夹闭阻断大鼠左肺门30min,开放后再灌注120min以复制肺缺血再灌注损伤模型。32只SD大鼠随机分为假手术（等容生理盐水）组、模型（等容生理盐水）组、水蛭醇提物（400mg／kg）组、水蛭水提物（400mg／kg）组。于术前3d腹腔注射给药,每天1次,连续3d。放射免疫法测定大鼠血浆血栓素B2（TXB2）和6酮前列腺素F1a（6-keto-PGF1a）含量[可反映血栓素A2（TXA2）、前列环素（PGI2）水平];酶联免疫吸附法测定大鼠血清一氧化氮（NO）含量与一氧化氮合酶（NOS）活性。结果：与假手术组比较,模型组大鼠血浆中TXB2含量显著增加,TXB2／6．keto-PGF1a比值显著降低,血清中NO含量显著增加,NOs活性显著增强（P〈0．01或P〈0．05）;与模型组比较,水蛭醇提物组、水蛭水提物组大鼠血浆TXB2、6-keto-PGF1a含量显著减少,TXB2／6．keto—PGF1a比值显著升高,血清N0含量显著减少,NOS活性显著减弱（P〈0．01或P〈0．05）,且以上指标水蛭醇提物组均好于水蛭水提物组,但差异无统计学意义（P〉0．05）。结论：水蛭醇提物与水蛭水提物均可降低肺缺血再灌注模型大鼠TXA2、PGI2、NO含量和NOS活性,且前者效果好于后者。     

六味地黄方对高脂血症大鼠血浆 ET、TXA2、PGI2水平及动脉内皮保护的影响

目的：研究六味地黄方对高脂血症大鼠血浆ET、TXA2、PGI2水平及动脉血管内皮保护的影响。方法：通过高脂饮食建立高脂血症大鼠模型,观察大鼠外周循环内皮细胞（CEC）、主动脉病理学、内皮素（ET）、前列腺素I2（PGI2）、血栓素A2（TXA2）的变化。结果：六味地黄方能减少高脂血症大鼠外周CEC及主动脉内皮细胞损伤;降低高脂大鼠血清ET、血浆TXA2,升高血浆PGI2水平。结论：六味地黄方对高脂血症大鼠内皮细胞具有保护作用,其作用机制可能与改善内皮细胞分泌功能有关。     

丹参注射液对妊娠高血压综合征患者血浆TNF-á和TXA2/PGI2平衡的调节作用

目的 观察丹参注射液治疗前后妊娠高血压综合征(PIH)患者血清TNF-α变化和血浆血栓素A2(TXA2)/前列环素(PGI2)平衡变化情况,探讨其治疗PIH的作用机制.方法 选择40例轻中度PIH患者,予以丹参注射液8mL静滴10d(丹参治疗组),同时另取正常妊娠40例做对照.ELISA双抗体夹心法检测丹参治疗组治疗前后TNF-α的含量变化,放射免疫法测定治疗前后血浆中TXA2、PGI2其稳定代谢产物TXB2和6-keto-PGF1α的浓度作为判断TXA2和PGI2含量的指标;同时测定正常妊娠对照组的TNF-α、TXB2和6-keto-PGF1α的含量作为比较.结果 与正常妊娠对照组相比较,治疗前丹参治疗组患者血清TNF-α含量升高(P＜0.05);血浆TXA2含量升高(P＜0.05),而血浆PGI2含量降低(P＜0.05),TXA2/PGI2比值升高.经过丹参注射液治疗10d后,与治疗前相比较,血清TNF-á含量有所下降(P＜0.05);血浆TXA2含量有所下降(P＜0.05),血浆PGI2含量有所上升(P＜0.05),TXA2/PGI2比值下降.结论 PIH病程中存在TNF-α水平升高和TXA2/PGI2比值升高.丹参治疗PIH的作用机制可能是通过降低患者血清TNF-α含量,使血管内皮通透性恢复;同时纠正血管活性物质分泌失衡,使血浆TXA2含量下降,血浆PGI2含量上升,TXA2/PGI2比值失衡恢复,最终使妊娠高血压综合征病程得以逆转.     

二参颗粒对心肌缺血大鼠血清TXA2/PGI2的平衡及炎症细胞因子水平的影响

摘要：目的:通过检测二参颗粒对心肌缺血大鼠血清学相关指标的影响,探讨二参颗粒抗心肌缺血的机制。方法:将50只健康Wistar大鼠按随机数字表法分为5组:正常对照组、模型组、二参颗粒高、中、低剂量组(35.2,17.6,8.8 g·kg-1),每组10只。连续灌胃给药2周后,除正常对照组外,其余4组大鼠用垂体后叶素(20 U·kg-1)腹腔注射建立心肌缺血模型后记录心电图标Ⅱ导联变化,TUNEL染色观察大鼠心肌细胞凋亡情况,检测血清血栓素A2（TXA2）、前列环素（PGI2）的含量及炎症细胞因子白细胞介素1（IL-1）、白细胞介素6（IL-6）和白细胞介素10（IL-10）的水平。结果:与正常对照组相比,模型组各时间点ST段J点变化值及T波变化值、心肌细胞凋亡指数、血清TXA2含量、IL-1及IL-6水平明显增加,PGI2含量、IL-10水平明显降低（P<0.05）。与模型组相比,二参颗粒部分剂量组各时间点ST段J点变化值及T波变化值显著降低,3个剂量组心肌细胞凋亡指数、血清TXA2含量、IL-1及IL-6水平显著降低,PGI2含量、IL-10水平显著增加（P<0.05）。结论:二参颗粒能调节TXA2/PGI2的平衡,改善血清炎症细胞因子水平,从而抑制血管内皮炎症性改变,保护血管内皮功能,达到抗心肌缺血作用。     

脂肝泰胶囊对高脂血症性脂肪肝大鼠血浆及肝组织血栓素B2和6—酮—前列腺素F1α含量的影响

目的：探讨脂肝泰胶囊治疗高脂血症性脂肪肝的作用机制。方法：采用高脂饮食喂饲大鼠复制脂肪肝模型，实验分组为模型组、脂肝泰高剂量组、脂肝泰低剂量组、东宝肝泰对照组和正常对照组。以高、低剂量脂肝泰和东宝肝泰进行干预，然后测定各组大鼠血浆、肝组织中血栓素B2（TXB2）及6－酮－前列腺素F1α（6－Keto-PGF1α)的含量。结果：模型组大鼠血浆、肝组织中TXB2和6－Keto-PGF1α的含量及其比值均较正常组明显升高（P＜0．05或P＜0．01）。与模型组比较，各治疗组大鼠血浆、肝组织中TXB2和6－Keto-PGF1α的含量及其比值均明显降低（P＜0．05或P＜0．01）；脂高组、脂低组血浆和肝组织TXB2和6－Keto-PGF1α含量及其比值均低于对照组（P＜0．05）。结论：脂肝泰胶囊可通过降低TXB2和6－Keto-PGF1α含量发挥治疗作用。     

Opposite effects of nicotinic acid and pyridoxine on systemic prostacyclin,thromboxane and leukotriene production in man

The effects of nicotinic acid (2500 mg orally during 12 hr) and pyridoxine (300 mg orally twice daily for seven days) on the excretion of urinary 2,3-dinor-6-ketoprostaglandin F1alpha, 11-dehydrothromboxane B2 and leukotriene E4, the markers of systemic prostacyclin, thromboxane A2 and cysteinyl leukotriene production, respectively, were investigated in healthy male volunteers (n=6-8). Nicotinic acid increased 11-dehydrothromboxane B2 and leukotriene E4 excretions to 2.6- and 2.0 times the initial values (P<0.05), respectively. In the volunteers treated with pyridoxine, 11-dehydrothromboxane B2 and leukotriene E4 excretions were decreased to 70% (P<0.05) and 65% (P<0.01) of the initial values, respectively, but the excretion of 2,3-dinor-6-ketoprostaglandin F1alpha was increased 1.7 times (P<0.01). The results suggest that nicotinic acid increases thromboxane and leukotriene synthesis which may not be beneficial for patients with cardiovascular diseases or asthma. In contrast, the increase in prostacyclin production and the inhibition in thromboxane and leukotriene synthesis by pyridoxine might be beneficial in disorders where the production of prostacyclin is decreased and the formation of thromboxane and cysteinyl leukotrienes is enhanced.     

Mechanisms underlying ATP-induced endothelium-dependent contractions in the SHR aorta

In mature spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats, acetylcholine, the calcium ionophore A 23187 and ATP release endothelium-derived contracting factor (EDCF), cyclooxygenase (COX) derivatives that activate thromboxane-endoperoxide (TP) receptors on vascular smooth muscle. The EDCFs released by acetylcholine have been identified as prostacyclin and prostaglandin (PG) H(2) while in response to A 23187 thromboxane A(2), along with the two other prostaglandins, contributes to the endothelium-dependent contractions. The purpose of the present study was to identify the EDCFs produced by ATP. Isometric tension and the release of prostaglandins were measured in isolated aortic rings of WKY rats and SHR. ATP produced the endothelium-dependent release of prostacyclin, thromboxane A(2) and PGE(2) (PGI(2)>TXA(2)> or =PGE(2)>PGF(2alpha)) in a similar manner in aorta from WKY rats and SHR. In SHR aortas, the release of thromboxane A(2) was significantly larger in response to ATP than to acetylcholine while that to prostacyclin was significantly smaller. The inhibition of cyclooxygenase with indomethacin prevented the release of prostaglandins and the occurrence of endothelium-dependent contractions. The thromboxane synthase inhibitor dazoxiben selectively abolished the ATP-dependent production of thromboxane A(2) and partially inhibited the corresponding endothelium-dependent contractions. U 51605, a non-selective inhibitor of PGI-synthase, reduced the release of prostacyclin elicited by ATP but induced a parallel increase in the production of PGE(2) and PGF(2alpha), suggestive of a PGH(2)-spillover, which was associated with the enhancement of the endothelium-dependent contractions. Thus, in the aorta of SHR, endothelium-dependent contractions elicited by ATP involve the release of thromboxane A(2) and prostacyclin with a possible contribution of PGH(2).     

Evaluation of the effects of anti-thromboxane agents in platelet-vessel wall interaction

We evaluated the capacity of anti-aggregating agents to influence thromboxane A(2) and prostacyclin formation, arachidonic acid-endoperoxide redirection, platelet aggregation and vessel tone, in isolated rabbit aorta incubated with homologous platelets. Picotamide (N,N'bis(3-pyridinylmethyl)-4-methoxy-isophthalamide), the only dual thromboxane A(2)-synthase inhibitor/receptor antagonist in clinical use, inhibited arachidonic acid-induced platelet aggregation with low potency, increased 180-fold by aorta presence. It inhibited thromboxane A(2) formation in platelets and, in aorta presence, increased prostacyclin formation. Ozagrel (OKY-046, (E)-3-(4-(1-imidazolylmethyl)phenyl)-2-propenoic acid), a pure thromboxane A(2)-synthase inhibitor, behaved similarly to picotamide, although the aorta caused a higher (600-fold) shift. The potency of the antagonist SQ 29,548 (1S-(1 alpha,2 beta(5Z),3 beta,4 alpha))-7-(3((2-((phenylamino)carbonyl)hydrazino)methyl)-7-oxabicyclo(2.2.1)hept-2-yl)-5-heptenoic acid) was unaffected by aorta. In coincubation experiments, arachidonic acid-challenge increased thromboxane A(2)-dependent vessel tone; picotamide increased prostacyclin and reduced thromboxane A(2) formation and vasoconstriction. Ozagrel mimicked picotamide; aspirin (acetylsalicylic acid) reduced aorta contractility, thromboxane A(2) and prostacyclin formation. SQ 29,548 reduced vasoconstriction without affecting eicosanoids. We demonstrate the importance of redirection of eicosanoids in the mechanism of action of thromboxane A(2) inhibitors/antagonists within platelet-vascular wall interactions. These findings bear relevance in the development of novel anti-thrombotic drugs.     

Inhibition by ethanol and mepacrine of phospholipase-dependent prostaglandin release from the isolated perfused rat lung

To investigate the possibility that millimolar concentrations of ethanol have a membrane-directed inhibitory effect on phospholipase A2 and prostanoid generation (suggested from previous platelet experiments), we studied the release of prostacyclin, thromboxane A2 and prostaglandin E2 from isolated perfused rat lung. Prostanoid release was evoked by arachidonic acid, bradykinin and ionophore A23187 and was measured after extraction by radioimmunoassay. In these experiments, prostanoid release is dependent upon biosynthesis from fatty acid precursors as there is no endogenous prostanoid storage pool. Arachidonic acid and bradykinin caused enhanced release of more prostacyclin than thromboxane A2 with much less prostaglandin E2 and no detectable prostaglandin F2 alpha, whereas A23187 released equal proportions of prostacyclin and thromboxane A2 with less prostaglandin E2. Ethanol at 50 mM resembled mepacrine (46 microM) in that prostanoid release in response to bradykinin and A23187 was highly significantly reduced with little effect on release induced by arachidonic acid. We suggest that ethanol, like mepacrine, interferes with prostaglandin generation by an action at the phospholipase step. This may be secondary to a physical effect on membrane configuration.     

URINARY EXCRETION OF PROSTANOIDS DURING SLEEP IN OBSTRUCTIVE SLEEP APNOEA PATIENTS

1. Given the unexplained frequent association between systemic hypertension and obstructive sleep apnoea (OSA), the secretion of prostanoids during sleep was investigated (more specifically, the ratio of prostacyclin (PGI2) to thromboxane A2 (TxA2), since they have marked opposite effects on vascular tone). Prostacyclin has vasodilating effects, whereas thromboxane results in vasoconstriction. 2. In 11 OSA drug-free male patients (age 53 +/- 2 years, mean +/- s.e.m.; apnoea index 55 +/- 15 apnoeas/hour of sleep; body mass index 31 +/- 2 kg/m2), we measured the urinary excretion during sleep of 6-keto-PGF1-alpha and of thromboxane TxB2 (the stable metabolites of prostacyclin PGI2 and of thromboxane A2 respectively). This was done on two consecutive nights; one untreated, the other with nasal continuous positive airway pressure (CPAP) treatment. The results were compared with those of nine normal unobese male subjects. 3. The urinary ratio of 6-keto-PGF1-alpha to TxB2 was significantly (P less than 0.001) lower in the untreated OSA patients (1.7 +/- 0.2) than in the controls (3.1 +/- 0.3). It significantly increased with CPAP treatment to 2.3 +/- 0.2, P less than 0.02, which was no longer different from the controls. 4. These results suggest that OSA is associated with an abnormal release of prostanoids during sleep resulting in a decrease of the prostacyclin to thromboxane ratio which potentially has a vasoconstricting effect. The relationship between these changes and the systemic hypertension often observed in OSA patients remains to be established.     

Effects of nonsteroidal anti-inflammatory drugs on prostacyclin and thromboxane in the kidney

Dose-response curves were obtained relating the effects of increasing amounts of aspirin, a nonselective cyclooxygenase (COX) inhibitor, and celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, on the concentrations of prostacyclin and thromboxane in renal cortex and medulla of rabbits. The concentrations of the two agonists (aspirin and celecoxib) which elicit a half-maximal response on the prostanoid concentration (EC(50)) were compared. Additionally, controls for prostacyclin and thromboxane were related to values for the experimental groups. The EC(50) values for celecoxib were considerably lower than those for aspirin, indicating that celecoxib was more effective in suppressing prostanoid production. There were also significant differences between the majority of experimental groups and their respective controls, further evidence for the greater inhibitory activity of celecoxib on prostacyclin. Celecoxib lowered the ratio prostacyclin/thromboxane in the renal medulla; mercuric chloride further diminished the concentration of prostacyclin in the renal medulla. The results confirm that in the normal rabbit kidney, both nonselective and specific COX inhibitors interfere with renal prostanoid synthesis, but that a selective COX-2 inhibitor is more effective.     

New trends in thromboxane and prostacyclin modulators

Thromboxane A2 (TXA2) and prostacyclin (PGI2) are two labile products formed from arachidonic acid by the way of cyclooxygenase. An overproduction of thromboxane A2 has been detected in a series of diseases whereby this prostanoid is assumed to contribute to the underlying pathomechanisms by its potent stimulation of platelet aggregation and smooth muscle contraction. This increased TXA2 biosynthesis is frequently accompanied by a stimulation of prostacyclin formation which is one of the most potent inhibitors of platelet aggregation and smooth muscle contraction. Therefore, TXA2 / prostaglandin endoperoxide H2 receptor antagonists, thromboxane synthase inhibitors and drugs which combine both activities have been developed with the aim to suppress the formation and/or the action of thromboxane A2. Since prostacyclin has been demonstrated to counterbalance the pathological effects of TXA2, several PGI2 agonists have also been developed. This review will highlight the evolution and some of the latest findings in the field of prostacyclin and thromboxane A2 modulators mainly those which are under clinical evaluation or marketed.     

Shifts in the affinity distribution of one class of seven-transmembrane receptors by activation of a separate class of seven-transmembrane receptors

We have demonstrated previously that activation of thrombin receptors causes increased Galpha(q) coupling to thromboxane A(2) receptors and increased thromboxane A(2) receptor ligand affinity. These results led to the hypothesis that thrombin receptor activation stimulates Galpha(q) redistribution to thromboxane A(2) receptors, thereby shifting them to a higher affinity state. The present study investigated three questions regarding this inter-receptor signaling phenomenon: (i) does activation of thrombin receptors cause a redistribution of thromboxane A(2) receptor subpopulations; (ii) does inter-receptor signaling require that participating receptors couple to the same family of G-protein alpha-subunits; and (iii) does inter-receptor signaling occur in cell types other than platelets? It was found that thrombin receptor activation caused a shift in the thromboxane A(2) receptor binding data from a one-site model to a two-site model (K(i) = 0.5 microM vs K(i) = 10 nM and 1.1 microM for the antagonist 4-[2-[[(4-chlorophenyl)sulfonyl]amino]ethyl]benzeneacetic acid (BM13. 505) and K(i) = 2.5 microM vs K(i) = 29.5 nM and 2.6 microM for the agonist 9,11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F(2alpha) (U46619). It also was found that activation of prostaglandin D(2) receptors also caused a shift of prostacyclin receptor binding data from a one-site model (IC(50) = 10.1 nM) to a two-site model (IC(50) = 3.3 and 12.5 nM). The physiological manifestation of this inter-receptor signaling between prostacyclin and prostaglandin D(2) receptors was a synergistic inhibition of human platelet aggregation. Finally, the present results established that activation of endothelial cell thrombin receptors shifts thromboxane A(2) receptor affinity from K(i) = 0.8 microM (control) to K(i) = 0.2 microM (thrombin receptor-activating peptide), indicating that cells other than platelets have the capability to signal between seven-transmembrane receptors.     

In vitro biosynthesis of cyclooxygenase metabolites in ovalbumin-sensitized and control lungs of guinea pigs

Cyclooxygenase metabolism may regulate mediator release in anaphylaxis. The in vitro biosynthesis of cyclooxygenase metabolites was examined, using isolated microsomal membranes from ovalbumin-sensitized and control guinea pig lungs, under conditions in which the substrate concentration ([³H]arachidonic acid) was varied (5–168 μM). With microsomes from sensitized lungs, there was stimulation of cyclooxygenase activity at substrate concentrations from 20 to 100 μM, with the major increases in activity occurring in the biosynthesis of thromboxane B₂ and prostaglandin D₂. At substrate concentrations greater than 100 μM, the biosynthesis of thromboxane B₂ and prostaglandin D₂ decreased in microsomes of sensitized lungs to the level of production found in control-lung microsomes. In contrast, prostacyclin production was significantly higher in the control-lung microsomes at the higher substrate concentrations. The ratio of prostacyclin to thromboxane production was lower in sensitized-lung microsomes at all substrate concentrations. No changes in the biosynthesis of prostaglandins F_2α or E₂ were detected between the two groups. Kinetic analysis of the data demonstrated that the cyclooxygenases in control and sensitized-lung microsomes exhibited different apparent K_m and V_max values. When the enzymes from both the control and the sensitized-lung microsomes were assayed in the presence of indomethacin (1–10 μM), a cyclooxygenase inhibitor, thromboxane synthesis was preferentially inhibited. The microsomal enzymes from control and sensitized lungs showed similar responses to the drug. At the indomethacin concentrations used, no significant inhibition of prostacyclin or prostaglandin production occurred. The results of these in vitro experiments support the hypothesis that net changes in the biosynthesis of cyclooxygenase metabolites may modulate the anaphylactic response of the lungs in sensitized animals.