Inositolphosphate formation in thoracic and abdominal rat aorta following Gq/11-coupled receptor stimulation.

Although thoracic and abdominal rat aorta are often used as a classical pharmacological preparation for the assessment of vascular drug effects, little is known on regional differences among these two parts of the aorta with regard to their reaction to Gq/11-coupled receptor activation. Thus, we determined, in rings from thoracic and abdominal aorta from 12-week-old male Wistar rats, the effects of noradrenaline (NA; 10(-8)-10(-4) M), endothelin-1 (ET-1; 10(-10)-10(-6) M) and the thromboxane A2 mimetic U 46619 (10(-8)-10(-5) M) on inositolphoshate (IP) formation (assessed as accumulation of total [3H]IPs in [3H]myoinositol prelabelled rings). NA, ET-1 and U 46619 concentration-dependently increased IP formation; maximum increases were, however, significantly more pronounced in thoracic than in abdominal aorta. Similarly, NA, ET-1 and U 46619 evoked significantly larger maximum contractions in thoracic than in abdominal aorta. NA-induced [3H]IP formation could be inhibited with BMY 7378 (10(-9)-10(-4) M) and with 5-methyl-urapidil (5-MU; 10(-9)-10(-5) M) both exhibiting biphasic concentration-inhibition curves. The pKi-values for BMY 7378 at the high affinity site were in thoracic aorta 8.93+/-0.28 (n=5), and in abdominal aorta 8.76+/-0.35 (n=4) and at the low affinity site 6.45+/-0.2 (thoracic aorta) and 6.55+/-0.27 (abdominal aorta). pKi-Values for 5-MU in thoracic aorta at the high affinity site were 8.25+/-0.34 (n=4), and at the low affinity site 6.61+/-0.39 . In abdominal aorta reliable pKi-values could not be calculated for 5-MU due to a low signal-to-noise ratio. On the other hand, in both preparations the ETA-receptor antagonist BQ-123 (10(-9)-10(-5) M) and the TP-receptor antagonist SQ 29548 (10(-9)-10(-5) M) inhibited ET-1- and U 46619-induced IP formation, respectively, with monophasic concentration-inhibition curves: pKi-values for BQ-123 were: 8.16+/-0.24 (thoracic aorta) and 8.10+/-0.35 (abdominal aorta) and for SQ 29548: 8.2+/-0.3 (thoracic aorta) and 8.5+/-0.3 (abdominal aorta). The amount of immunodetectable Gq/11-protein was similar in both tissues. We conclude that responses to NA, ET-1 and U 46619 (IP formation and contractile force) are larger in thoracic than in abdominal aorta. ET-1 effects on IP formation are mediated by ETA-receptors and U 46619 effects by TP-receptors. NA effects are mediated by alpha1D- and alpha1A-adrenoceptors; alpha1B-adrenoceptors seem to play a minor role.

The cardiac beta-adrenoceptor-G-protein(s)-adenylyl cyclase system in monocrotaline-treated rats.

In rats, injection of the alkaloid monocrotaline (MCT) causes right ventricular hypertrophy and cardiac failure. In order to study whether, in MCT-treated rats, changes in the cardiac beta -adrenoceptor-G-protein(s)-adenylyl cyclase system might be comparable to those found in human primary pulmonary hypertension, we assessed in right and left ventricles from MCT-treated rats the components of the beta -adrenoceptor system: the receptor number and subtype distribution (by (-)-[(125)I]iodocyanopindolol binding), the G-proteins (by quantitative Western blotting), and the activity of adenylyl cyclase. A single injection of 60 mg/kg i.p. MCT caused in rats right ventricular hypertrophy (RVH); part of the rats developed cardiac failure (RVF). In these rats the cardiac beta -adrenoceptor-G-protein(s)-adenylyl cyclase system was markedly changed beta -adrenoceptors were desensitized due to a decrease in receptor number, an uncoupling of the receptor from the G(s)-adenylyl cyclase system, a decrease in G(s)and a decrease in the activity of the catalytic unit of adenylyl cyclase. In general, these changes were more pronounced in right ventricles v left ventricles, and in rats with RVF v rats with RVH. On the other hand, cardiac muscarinic receptors and G(i)appeared not to be altered. We conclude that in MCT-treated rats changes in the cardiac beta -adrenoceptor-G-protein(s)-adenylyl cyclase system occur that resemble those observed in human primary pulmonary hypertension. Thus, MCT-treated rat appears to be a suitable animal model to study in more detail the pathophysiology of the development of right heart failure, and to identify new therapeutic possibilities.

Differential pattern of endothelin-1-induced inotropic effects in right atria and left ventricles of the human heart.

In human right atrium, endothelin A (ET(A)) receptors couple to both inositol phosphate formation and inhibition of adenylylcyclase, whereas in human left ventricle, ET(A) receptors couple only to inositol phosphate formation. To find out whether this might be of functional relevance, we studied, in right atria obtained from 32 patients undergoing coronary bypass grafting without apparent heart failure, and in right atria and left ventricles from eight patients with end-stage heart failure (NYHA IV) undergoing heart transplantation, the effects of endothelin-1 (ET-1) on basal force of contraction or on force of contraction increased by 1 microM forskolin. ET-1 (0.1 microM) exerted a positive inotropic effect in atrial and ventricular tissue; this could be antagonized by the ET(A)-receptor antagonist BQ 123, but not by the ET(B)-receptor antagonist BQ 788. In atrial, but not in ventricular tissue, this positive inotropic effect was preceded by a transient negative inotropic effect. This negative inotropic effect was inhibited by BQ 123, but not by BQ 788. It was significantly prolonged in forskolin-prestimulated atria, and was significantly larger in atria from failing hearts. We conclude that, because ET-1 inhibits adenylylcyclase and causes negative inotropic effects in atria but not in ventricles, adenylylcyclase inhibition might be responsible for the transient negative inotropic effect of ET-1.

FP-receptor mediated trophic effects of prostanoids in rat ventricular cardiomyocytes.

The aim of this study was to characterize the receptor subtype involved in cardiac effects of prostanoids. For this purpose we determined in neonatal and adult rat cardiomyocytes effects of prostanoids on inositol phosphate (InsP)-formation (assessed as accumulation of total [(3)H]-InsP's in myo-[(3)H]-inositol pre-labelled cells) and on rate of protein synthesis (assessed as [(3)H]-phenylalanine incorporation), and on contractile force in left ventricular strips of the rat heart. For comparison, effects of prostanoids on InsP-formation and contractile force were determined in rat thoracic aorta, a classical TP-receptor containing tissue. Prostanoid increased InsP-formation and rate of protein synthesis in neonatal as well as adult rat cardiomyocytes; the order of potency was in neonatal (PGF(2alpha)>PGD(2)> or =PGE(2)> or =U 46619>PGE(1)) and adult (PGF(2alpha)>PGD(2)> or =PGE(2)>U 46619) rat cardiomyocytes well comparable. Moreover, in electrically driven left ventricular strips PGF(2alpha) caused positive inotropic effects (pD(2) 7.5) whereas U 46619 (up to 1 microM) was uneffective. In contrast, in rat thoracic aorta U 46619 was about 100 times more potent than PGF(2alpha) in increasing InsP-formation and contractile force. The TP-receptor antagonist SQ 29548 only weakly antagonized prostanoid-induced increases in rate of protein synthesis (pK(B) about 6) in rat cardiomyocytes but was very potent (pK(B) about 8-9) in antagonizing prostanoid-induced increases in InsP-formation and contractile force in rat aorta. We conclude that, in cardiomyocytes of neonatal and adult rats, the prostanoid-receptor mediating increases in InsP-formation and rate of protein synthesis is a FP-receptor. Moreover, stimulation of these cardiac FP-receptors can mediate increases in contractile force.

Muscarinic receptors in the failing human heart.

In the human heart, as in the heart of several other species, muscarinic receptors are predominantly of the M2-subtype that couple via a pertussis toxin-sensitive Gi-protein to inhibit adenylyl cyclase. However, it is not clear whether an additional muscarinic receptor subtype exists in the human heart. In human right atrium, stimulation of muscarinic M2 receptors causes direct negative inotropic and chronotropic effects; in human ventricular myocardium, however, the negative inotropic effect can be only achieved when basal force of contraction has been pre-stimulated by cyclic AMP-elevating agents such as beta-adrenoceptor agonists, forskolin or phosphodiesterase inhibitors (indirect effect); this has been shown in various in vitro and in vivo studies. Evidence has accumulated that in chronic heart failure vagal activity is decreased. Cardiac muscarinic M2 receptor density and functional responsiveness (inhibition of adenylyl cyclase activity and negative inotropic effects), however, are not considerably changed when compared with non-failing hearts although cardiac Gi-activity is increased.

Age-dependent decrease in the negative inotropic effect of carbachol on isolated human right atrium.

On isolated, electrically driven human right atrial strips, carbachol (10(-8)-10(-3) M) concentration-dependently decreased force of contraction prestimulated with 1 microM forskolin; maximal negative inotropic effects of carbachol (10(-6)-3 x 10(-6) M), however, were in atria from patients aged < 25 years (mean age: 16.8 +/- 2.0 years, n = 9) significantly larger than in patients aged 50-69 years (mean age: 62.5 +/- 0.7 years, n = 33) and were further decreased in patients aged > 70 years (mean age: 73.8 +/- 0.6 years, n = 11). We conclude that, in human right atrium, the recently described age-dependent decrease in muscarinic M2 receptor density is accompanied by a decrease in negative inotropic effects.

[Consensual inflammatory reaction in chemical eye burn of the rabbit eye]. / Untersuchungen zur konsensuellen Entzündungsreaktion bei Verätzung des Kaninchenauges.

BACKGROUND: Consensual ocular response has been known to occur following intracranial stimulation of the trigeminal nerve, intracameral injection of prostaglandins and other substances, after paracentesis and contusio bulbi. MATERIAL AND METHOD: We have examined the prostacyclin formation in both eyes after experimental alcali burn (0.25 mo/l NaOH) on 30 rabbits with ELISA over a follow up period of 14 days. RESULTS: After the alcali burn the aqueous prostacyclin level on the right eye is increased from 327 pg/ml aqueous to 27098 pg/ml aqueous, but on the left it stays normally. In conjunctiva and anterior uvea we measured normal amounts of prostacyclin. CONCLUSIONS: We could not find a consensual increase in prostacyclin formation in the anterior part of the fellow eye following alcali burn.

[Effect of non-steroidal anti-inflammatory drugs on inflammatory reaction. An animal experiment study]. / Zum Einfluss nichtsteroidaler Antiphlogistika auf die Entzündungsreaktion. Eine tierexperimentelle Studie.

Previous investigations indicate that the application of a cyclooxygenase inhibitor alone can lead to amplification of the inflammatory process. To prevent this response a combination of flurbiprofen and leukotriene receptor antagonist (S 872419 A, Hoechst AG, Frankfurt/Main) were tested in an animal model. The right eye of 48 rabbits was burned with alcali (0.25 mol/l sodium hydroxide). Thirty animals were treated with (0.03% flurbiprofen sodium eye drops and 1% S872419 A eye drops, five times daily). Eighteen animals received no therapy for up to 14 days. Hyperemia of the limbal vessels, corneal vascularization, the number of PMNLs in the cornea and the prostacyclin level in the anterior chamber of the eye (ELISA) served as criteria. On day 3, after the chemical burn only the therapy group showed a significant decrease in hyperemia of the limbal vessels (14th day: score with therapy 0.3, without 2.17, P < 0.05). Without therapy corneal vascularization filled a much larger area from the 6th day on (14th day: area with therapy 3.5 mm2, without 63.7 mm2, P < 0.05). The number of PMNLs was effectively limited by therapy in the superficial stromal layers of the cornea and with therapy showed 2.4 cells/0.014 mm2 and without 18 cells/0.014 mm2 after 48 h. Without Therapy the level of prostacyclin was up to 15 times higher than with (12-h value with therapy) 607 pg/ml, without 9094 pg/ml, P < 0.05). Suppression of cyclo- and lipoxygenase-mediated inflammatory responses is possible with the combination of flurbiprofen and S 872419 A when two arachidonic by inhibition of prostanoid synthesis and leukotriene receptor block at the same time.

PAF effects on eicosanoid release in neonatal rat cardiomyocytes.

The aim of this study was to find out whether, in neonatal rat cardiomyocytes, platelet-activating factor (PAF) can stimulate eicosanoid formation. For this purpose neonatal cardiomyocytes were incubated for 60 min at 37 degrees C in HANKS buffer with PAF (10-1000 nM), and the eicosanoids thromboxane A2 (TXA2) and prostacyclin (PGI2) were assessed in the supernatant as TXB2 and 6-keto-PGF1 alpha, respectively, by an enzyme immunoassay. PAF caused concentration-dependent release of PGI2; TXA2, however, was significantly released only at the highest concentration of PAF (1000 nM). Acetylsalicylic acid (556 microM) and the PAF antagonist WEB 2086 (10 microM) significantly attenuated PAF-induced eicosanoid formation. We conclude that in neonatal rat cardiomyocytes PAF can induce eicosanoid formation and this effect is brought about by activation of a specific PAF receptor.

Effects of PAF on cardiac function and eicosanoid release in the isolated perfused rat heart: comparison between normotensive and spontaneously hypertensive rats.

The aim of this study was (a) in isolated perfused rat heart to characterize the effects of platelet-activating factor (PAF) on coronary flow, ventricular contractility, and eicosanoid release and (b) to determine whether PAF effects are altered in hearts from spontaneously hypertensive rats (SHR). PAF (10(-10)-10(-7) mol) dose-dependently decreased coronary flow and ventricular contractility; concomitantly, coronary effluent concentrations of thromboxane (TX)B2 and prostaglandin F2 alpha (PGF2 alpha) were elevated but not those of prostacyclin. The PAF receptor antagonist WEB 2086 (10(-7)-10(-5) mol/l) concentration-dependently antagonized these PAF effects. In addition; the cyclo-oxygenase inhibitor indomethacin (5 x 10(-5) mol/l) prevented PAF (10(-9)-10(-7) mol) induced eicosanoid release; in the presence of indomethacin PAF caused coronary constriction and ventricular depression only at the highest dose (10(-7) mol) but had no effect at 10(-9) or 10(-8) mol. Moreover, the TXA2 antagonist SQ29,548 (10(-6) mol/l) completely inhibited 10(-8) mol PAF induced ventricular depression but did not effect coronary constriction. In SHR PAF (10(-9)-10(-7) mol) evoked decreases in coronary flow and ventricular contractility did not differ from those in normotensive Wistar-Kyoto rats while PAF induced TXA2 and PGF2 alpha release was markedly enhanced. In addition, decreases in coronary flow and ventricular contractility induced by the TXA2 agonist U 46619 (10(-7) mol/l) were markedly depressed in SHR. We conclude that in isolated perfused rat heart PAF causes coronary constriction and depression of ventricular function mainly indirectly through released TXA2 and/or PGF2 alpha. Moreover, the fact that in SHR the PAF effects on coronary flow and ventricular function are not altered despite markedly enhanced TXA2 and PGF2 alpha release supports the view that in the SHR the receptors mediating TXA2 and/or PGF2 alpha effects are desensitized.

Relevance of mediators to cardiac parameters of isolated anaphylactic guinea-pig heart.

The release of histamine, eicosanoids and catecholamines were measured after induction of anaphylaxis in isolated guinea-pig hearts. The concentration-time profile of these mediators was compared with changes of cardiac parameters. The histamine and catecholamine levels of the coronary effluent were determined at 10 s intervals; thromboxane and prostacyclin levels at 60 s intervals. The release of histamine and norepinephrine were maximum between 20 and 30 s after the antigen challenge and decreased rapidly within 60 s. Thromboxane and prostacyclin increased to a maximum after 3 min and declined slowly within 10 min. The rise in histamine release was correlated with tachycardia. The release of thromboxane was correlated with the increase of coronary perfusion pressure. Cimetidine inhibited the tachycardia and clemastine reduced bradyarrhythmia. The inhibition of lipoxygenase and cyclooxygenase also reduced the rise in the perfusion pressure. These data suggest that different mediators are time-dependently involved in anaphylaxis-induced cardiac changes.

[Effect of diclofenac and flurbiprofen on the course of inflammation after cataract extraction]. / Zum Einfluss von Diclofenac und Flurbiprofen auf den Entzündungsverlauf nach der Kataraktextraktion.

In a prospective, randomized, double-blind study the effect of different anti-inflammatories (diclofenac 0.1%, flurbiprofen 0.03%) versus placebo on the intra- and postoperative inflammation in 65 eyes was examined. Prednisolone acetate 0.5% eye drops were the basic therapy in all three groups. As criteria served the difference between pre- and postoperative flare and cell concentration in the anterior chamber, measured using the laser flare cell meter, the clinical course, and the level of the inflammatory mediator 6-oxo-PGF1 alpha (prostacyclin) in the aqueous humor after intraoperative paracentesis, determined by means of enzyme-linked immunosorbent assay. The level of prostacyclin was not influenced in any of the three groups. The numbers of cells decreased continuously, but without marked differences among the groups. On the basis of the concentration of protein measured in the aqueous humor and the clinical course, diclofenac 0.1% proved to be a more potent additive anti-inflammatory therapy than flurbiprofen 0.03% immediately after the surgical procedure (P = 0.039 at 1 day after operation), but the final results (4 weeks after operation) revealed no detectable difference. By application of placebo, an obvious higher concentration of protein was measured during all the observations (P = 0.0002). Therefore in the case of cataract extraction the local steroidal therapy should be combined with nonsteroidal anti-inflammatory drugs (cyclooxygenase inhibitors).

von Willebrand's disease and hemophilia are associated with diminished thromboxane A2 (TXA2) formation in clotting whole blood.

Von Willebrand's disease (vWd) and hemophilia are associated with hemorrhagic diathesis and disturbances in platelet aggregation to vessel wall. We compared the time course of thromboxane A2 (TXA2) formation by platelets during spontaneous clotting of blood of patients with von Willebrand syndrome and from patients with hemophilia A or B with that of healthy controls which were matched for sex, age and serum lipid status. In clotting blood of healthy females the TXA2 production rose at 37 degrees C in 60 min up to 228.2 +/- 32.3 ng/ml. In patients with vWd the TXA2 production at 60 min was significantly lower (129.1 +/- 26.7 ng/ml, p < 0/05). In hemophilia type A and B the TXA2 formation after 5-30 min was significantly diminished in comparison to healthy male controls (p < 0.05). From the diminished amount of TXA2 formed during spontaneous clotting of whole blood we conclude that the activation of platelets of patients with von Willebrand syndrome or hemophilia type A and B is diminished as compared to healthy controls possibly caused by reduced formation of thrombin in the blood coagulation process.

Lipoproteins from normolipidemic and dyslipidemic subjects modify the thromboxane A2 generation by platelets in clotting human blood.

The study was performed to investigate the influence of lipoproteins (LP) on the thromboxane (TX) A2 formation capacity of platelets in clotting whole blood in vitro. The different lipoprotein fractions VLDL, LDL, HDL2 and HDL3 were isolated from blood of normo- or dyslipidemic volunteers by ultracentrifugation. These lipoproteins were incubated in blood with different levels of serum total cholesterol (TC) taken from normolipidemics (TC < 200 mg/dl), moderate hypercholesterolemics (TC: 200-250 mg/dl) or subjects with high cholesterol level (TC > 250 mg/dl), respectively. The amount of serum TXA2 formed within 60 min at 37 degrees C was measured by enzyme immunoassay. The results obtained show that the efficacy of separate LP fractions to influence the TXA2 production depends not only on the type of LP fraction but also on the source of plasma used for isolation of LP and on the cholesterol level in the blood for incubation: LDL taken from normolipidemics or moderate hyperlipidemics inhibited the TXA2 formation in blood from normolipidemics (P < 0.02, respectively), but enhanced it in blood from persons with moderate hypercholesterolemia (P < 0.05). LDL from hyperlipidemics enhanced TXA2 production in blood from hyperlipidemics (P < 0.05). The HDL2 fractions inhibited the TXA2 formation in blood from normo- and hypercholesterolemics (P < 0.02, resp.), but there was no effect of HDL2 in clotting blood from persons with moderate hypercholesterolemia. All HDL3 fractions tested inhibited the TXA2 formation in all types of blood used for clotting (P < 0.02, resp.), probably due to their great cholesterol accepting capacity.

Interactions of prostanoids with the platelet activating factors.

The platelet-activating factor (PAF) induced a marked increase of the thromboxane (TX) B2-formation in the incubation medium of isolated myocardium and tissue from other organs. The content of the 6-oxo-prostaglandin (PG)F1 alpha, the inactive metabolite of PGI2, remained uninfluenced or showed a small decrease. PAF, given in a concentration of 2.10(-9) mol/l or a single dose of 100 ng, significantly reduced the contraction force and the coronary flow of isolated guinea-pig hearts. This effect was connected with a high efflux of TXA2. The PAF-antagonist, WEB 2086, nearly abolished the cardiac effects of PAF, and iloprost or a pretreatment with indomethacin markedly reduced the PAF-influence on the heart. The TXA2-antagonist BM 13177 was ineffective. The results indicate a close interaction between the myocardial PAF-effect and the TXA2-formation of the heart tissue, but gave no suggestion for a mediation of the PAF-effect by TXA2. The PAF-antagonistic action of WEB 2086, iloprost and indomethacin could be of some interest in the therapy of cardiovasculatory diseases.

Relevance of vasoactive mediators for the blood pressure effects of intravenous arachidonic acid injection in rats.

Vasopressor response and release of eicosanoids following intravenous injection of arachidonic acid (AA) were examined in normotensive rats. AA administration caused a rapid initial fall of arterial pressure followed by a brief rise and a subsequent prolonged fall in anesthetized rats. Immediately after AA injection the blood levels of TXB2 and 6-keto-PGF1 alpha, the stable metabolites of TXA2 and prostacyclin, rose, from 1.52 +/- 0.23 ng/ml to 176.4 +/- 42.6 ng/ml and from 4.05 +/- 0.67 ng/ml to 171.4 +/- 31.2 ng/ml, respectively. Blood pressure behaviour and eicosanoid blood level were influenced by different inhibitors and antagonists of vasoactive mediators. The cyclooxygenase inhibitor acetylsalicylic acid completely eliminated the second blood pressure depression after AA injection and simultaneously diminished TXB2 and 6-keto-PGF1 alpha formation in murine blood, whereas the TXA2 receptor antagonist BM 13.177 prevented the return of the blood pressure to preinjection level after the initial brief fall in arterial pressure. Although the TXA2 synthase inhibitor HOE 944 markedly inhibited TXB2 formation, no influence on AA-induced blood pressure changes could be registered. The receptor antagonist of platelet activating factor BN 52021 and the serotonin and histamine receptor antagonist cyproheptadine also reduced TXB2 amounts, in murine blood without any effects on blood pressure behaviour.

Influence of HDL on the formation of 6-keto-PGF1 alpha and TXB2 in vitro: the importance of the source of HDL.

The influence of HDL, isolated from normolipidemic human blood and blood of normo- and hyperlipidemic rabbits, on in vitro 6-keto-PGF1 alpha synthesis by rabbit aorta and on TXB2 synthesis by platelets of clotting human and rabbit blood was tested. The HDL fraction from normolipidemic subjects, when incubated with blood from normolipidemic humans or rabbits, inhibited TXB2 formation. The same fraction stimulated the formation of 6-keto-PGF1 alpha after incubation with rabbit aorta taken from normolipidemic animals. HDL taken from hyperlipidemic rabbits inhibited 6-keto-PGF1 alpha formation in rabbits and had no influence on TXB2 formation. These results support the hypothesis that not only is the absolute amount of HDL important for its influence on prostanoid formation, but also the origin and the composition of the HDL fraction.

Influence of a cholesterol rich diet in rabbits on the formation of PGI2 and TXA2.

In the study was investigated whether the formation of prostanoids is changed in the different regions of aorta or in clotting whole blood in dependence on development of atherosclerosis. For this question New Zealand rabbits were fed for different periods with a cholesterol rich diet (0.5%). At the end of the different dietary periods the animals were killed and the following parameters estimated: blood: levels of total cholesterol, HDLcholesterol, VLDLcholesterol, cholesterol in the beta-migrating lipoprotein fraction, serum lipid peroxides, TXB2 formation capacity of clotting whole blood; aorta: surface of intima covered with fatty streaks, free and esterified cholesterol, triglycerides, collagen, formation of 6-keto-PGF1a and TXB2 by abdominal and thoracic aortas. The lipid parameter demonstrated a relatively strong correlation with the duration of cholesterol rich diet or the macroscopically detectable atherosclerosis, but the prostanoid formation remained unchanged.

Biosynthesis of TXB2 and 6-oxo-PGF1 alpha in the heart and other tissues under pathophysiological conditions.

Many organs have the capacity to form prostanoids. Under pathophysiological conditions the biosynthesis of TXB2 and 6-oxo-PGF1 alpha is markedly increased in the myocardium and the gastric mucosa. Tumor growth is linked with an enhanced prostanoid formation. Furthermore a rise of the PG content could be found in the liquor, aqueous humor and urine under diseases of the related organs. These results could be of some significance for diagnosis and therapy control.