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Biomedical subjects

C Giessler

Publications and source records attributed to C Giessler.

47 records · Page 3Linked to original sources
PubMed1983

[The modification of the biosynthesis and effect of thromboxane A2 and prostacyclin by trapidil (Rocornal)].

The influence of the antianginal drug trapidil on the biosynthesis of thromboxane A2 (TXA2) and/or prostacyclin (PGI2), metabolites of arachidonic acid (AA), was investigated in rabbit and human platelet rich plasma (PRP), in homogenates of rabbit spleen and of rat lung and in aortic preparations of rats and rabbits, respectively. Trapidil showed a marked inhibition of the AA-induced aggregation and TXA2 biosynthesis in rabbit and human PRP. The TXA2 inhibition by trapidil was not demonstrable in damaged platelets and seems to require intact cells. In homogenates of rat lungs, trapidil remained without effect on the TXA2 and PGI2 synthesis. In rabbit spleen homogenates the drug induced an inhibition of the formation of both AA metabolites. In contrast to Japanese authors we could not observe any increase in PGI2 release in rat aortic preparation. The PGI2 release from isolated perfused guinea pigs hearts was enhanced; on the other hand, the PGI2 efflux from rabbit hearts remained unchanged. The antiaggregatory effect of PGI2 on the ADP-induced aggregation was strengthened by trapidil, showing an overadditive effect in rabbit PRP. The aggregation inducing effect of the prostaglandin endoperoxide analog U-46619 was inhibited by trapidil. A possible clinical significance of the inhibitions of the synthesis and effect of TXA2 for therapy of ischemic heart disease is discussed.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1982

Studies of the influence of nitroglycerin on the synthesis of prostaglandins and thromboxane A2 and on platelet aggregation.

Nitroglycerin (NG) did not influence the synthesis of prostaglandins and thromboxanes in organs and microsomal fractions of various animal species (rat, pig, rabbit). NG is an inhibitor of platelet aggregation in vitro dependent on NG dose and platelet activator. NG is able to disaggregate ADP-induced platelet aggregation. An increased antiaggregatory effect was observed when a low concentration of PGI2 was combined with NG.

Animals↗
PubMed1981

[Stimulation of prostacyclin biosynthesis as a possible mechanism of action of dipyridamole (author's transl)].

In microsomes of pig aorta, isolated perfused hearts of guinea-pigs, rabbit vessel preparations and homogenates of rat lungs 2,6-bis-[bis-(beta-hydroxyethyl)-amino]-4,8-dipiper-idino-pyrimido-[5,4-d]pyrimidine (dipyridamole) application caused a marked stimulation of prostacyclin biosynthesis. The oxygen incorporation into arachidonic acid indicating cyclooxygenase and lipoxydase activity under the influence of lyophilised ram vesicle microsomes was increased by dipyridamole. The formation of malondialdehyde and thromboxane A2 in platelet rich plasma of rabbits remained uninfluenced. On the other side the formation of thromboxane A2 was moderately inhibited in homogenates of guinea-pig lungs. The arachidonic acid-induced thrombus formation and following death of rabbits remained uninfluenced. The results indicate that dipyridamole causes a relatively specific alteration of the prostaglandin metabolism stimulating the biosynthesis of prostacyclin but without effect or only moderate inhibition of the formation of thromboxane A2. These effects could be looked upon as an important mechanism for the cardiovascular action of the drug.

Animals↗
PubMedDate not supplied

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.

Animals↗
PubMedDate not supplied

The trapidil derivative AR 12456 protects against serum hyperlipidemia in guinea pigs.

The administration of the trapidil derivative AR 12465 (5 mg/kg body weight) intraperitoneally to hypercholesterolemic guinea pigs caused a stronger reduction in serum total cholesterol (TC) than trapidil (20 mg/kg, i.p.) or a vehicle injection (saline with 5% ethanol i.p.). The stronger reduction of TC is caused by a lower level in the sum of all beta-migrating lipoproteins and an enhanced level of high-density lipoprotein. The levels of free and esterified cholesterol were not changed in kidney and left cardiac ventricle, but significantly enhanced (P less than 0.05) in the liver of all groups fed a cholesterol-rich diet. The elevation in liver cholesterol was higher in the group treated with AR 12456 than in the group treated with trapidil or with vehicle. The treatment with AR 12456 diminished the ratio TXB2/6-keto-PGF1 alpha for the capacity of aorta to form these prostanoids. In conclusion, our data show that AR 12456 has a strong antilipidemic action in guinea pigs fed a cholesterol-rich diet.

3',5'-Cyclic-AMP Phosphodiesterases↗