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Biomedical subjects

H J Mest

Publications and source records attributed to H J Mest.

At least 73 records · Page 4Linked to original sources
PubMed1988

Decrease in arterial blood pressure in spontaneously hypertensive rats by the TXA2 receptor antagonist BM 13177 and by acetylsalicylic acid.

The effects of the selective TXA2 receptor antagonist BM 13177 and of the cyclooxygenase inhibitor acetylsalicylic acid on blood pressure and heart rate were investigated in anaesthetized spontaneously hypertensive rats (SHR). After intravenous injection of BM 13177 (60 mg/kg) there was a strong short-lasting decrease in arterial blood pressure (BP) with a maximum reduction of 21.6% in the third minute after injection. The heart rate was only slightly decreased. The formation of TXB2 and 6-keto-PGF1 alpha in serum, aorta thoracica, renal medulla, and renal cortex, which was determined by radioimmunoassay, was not altered by BM 13177. Pretreatment with acetylsalicylic acid (100 mg/kg) attenuated the BM 13177 induced reduction of blood pressure and heart rate in male, but not in female SHR. An intravenous application of acetylsalicylic acid (ASA) (100 mg/kg) resulted in a decrease of blood pressure and heart rate only in male rats. The extent of these effects was similar to that induced by BM 13177. A possible explanation for the different reactions of male and female animals might be sex differences in the sensitivity of cyclooxygenase in the aorta thoracica to ASA and/or in the balance of prohypertensive and antihypertensive prostanoids. TXA2 and other prostanoids seems to participate in the short-time regulation of BP in SHR.

Animals↗
PubMed1988

Is the level of steroid hormones in the low density lipoprotein (LDL) particles responsible for the prostaglandin I2 inhibitory potency of LDL?

In LDL fractions, isolated by ultracentrifugation, sexual hormones are detectable. LDL from male volunteers contained a significantly higher level of testosterone than LDL from female volunteers. This difference, however, is not responsible for the enhanced ability of LDL from men versus LDL from women to inhibit PGI2 formation. The importance of LDL testosterone is contradicted by the following results: Firstly, the PGI2 inhibitory potency of LDL is independent of the age of volunteers and the recentrifugation of isolated LDL fractions, but the level of testosterone is diminished with increasing age of volunteers and after recentrifugation. Secondly, LDL from hyperlipidemic men type II a did not inhibit PGI2 formation, but the level of testosterone in the LDL of these volunteers is significantly higher than in LDL from healthy men.

Adult↗
PubMed1988

Pharmacological management of an impending placental insufficiency.

By means of drug administration a further decrease of the placental circulation in premature sonographic maturity of the placenta could be prevented via influencing the TXA2/PGI2 balance. Treatment of premature sonographic placental maturity with 50 mg acetylsalicylic acid (ASA) per day and three times daily 100 mg Rocornal, respectively, resulted in a significant increase of the birth weights. In a second series of experiments, three groups were treated with 50 mg/day ASA or 250 mg ASA/once per week and three times/day 100 mg Rocornal, respectively, from the 18th or 20th week of gestation to the 35th week. Subsequently, they were compared to a group of untreated controls. The birth weights of all treated groups were statistically significantly higher. The underlying mechanism is suggested to be an improved microcirculation.

Aspirin↗
PubMed1988

Influence of pentoxifylline administered in vivo on the synthesis of PGI2 in human varicose veins.

The influence of pentoxifylline on the synthesis of prostacyclin (PGI2) was studied using human varicose veins removed by a stripping operation. Patients got 100 mg pentoxifylline iv. during the operation. The synthesis of PGI2 was studied according to the inhibition of the ADP-induced platelet aggregation without and with addition of substrate (100 ng prostaglandinendoperoxide H2) to the incubation fluid. There were no changes in the synthesis of PGI2 compared to control values.

Epoprostenol↗
PubMed1988

Myocardial biosynthesis of prostacyclin and the influence of cardiac loading and drugs.

Cardiac tissue from different parts of hearts from guinea pigs and rabbits have the capacity to rapidly synthesize prostacyclin (PGI2). Auricles show a higher PGI2-formation than ventricles. Addition of the endoperoxide PGH2 markedly enhanced the myocardial PGI2-biosynthesis. Furthermore many cardiotonic drugs induced a significant rise, but eicosanoids or cyclooxygenase inhibitors a marked reduction of the cardiac PGI2-formation. Acute pressure overload by graduated aortic stenosis, ischemia by coronary ligation or pacing with high frequency reduced the cardiac contractility. After aortic stenosis the myocardial PGI2-biosynthesis is lowered, but increased after coronary ligation or pacing. Under these conditions indomethacin, PGE1, iloprost, verapamil and trapidil markedly reduced the PGI2-biosynthesis and exert a protective effect in regard to cardiac damage. The results indicate that pathophysiological changes significantly influence the PGI2-biosynthesis of the heart. The drug induced inhibition of the myocardial PGI2-formation parallels a cardioprotective effect of these substances.

Animals↗
PubMed1988

Influence of the antianginal drug trapidil and its derivative AR 12463 on arachidonic acid liberation and thromboxane formation in thrombin-stimulated platelets.

The 5,7-disubstituted s-triazolo(1,5-a)pyrimidines (TPs) trapidil and AR 12463 inhibited the thrombin-induced Thromboxane (TX) formation in washed human platelets in a concentration-dependent manner (Ic50:trapidil 410 mumol/l and AR 12463 9 mumol/l). The arachidonic acid (AA) liberation measured in parallel was unchanged or only reduced to a small extent. The present study shows that the inhibition of TX formation by trapidil and AR 12463 is independent of AA liberation of platelets.

Antihypertensive Agents↗
PubMed1988

Effects of trapidil and trapidil derivatives on arachidonic acid and prostaglandin endoperoxide analogue U 46619-induced blood pressure changes in rats.

The influence of trapidil (T) and two selected 5,7-disubstituted s-triazolo (1,5-a)pyrimidine derivatives (TD: AR 12456 and AR 12463) on arachidonic acid(AA)- and prostaglandin endoperoxide analogue U 46619-induced blood pressure changes in normotensive rats was investigated in comparison with the cyclooxygenase inhibitor acetylsalicylic acid (ASA) and the thromboxane A2 (TXA2) antagonist BM 13177. ASA and AR 12456 completely eliminated the second blood pressure depression after injection of AA and simultaneously diminished TXA2, TXB2 and 6-keto-PGF1a formation in murine blood, whereas BM 13177 prevented the return of the blood pressure to preinjection level after the initial brief fall in arterial pressure. BM 13177 and AR 12463 reduced the rise in U 46619-provoked blood pressure by 75% and 58%, respectively. Trapidil had no effect on blood pressure changes stimulated by AA and U 46619.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1988

The arrhythmogenic effect of platelet activating factor (PAF) is inhibited by PAF antagonist and by substances influencing eicosanoids.

Platelet-activating factor (PAF) induced arrhythmogenic effects in ouabain-induced arrhythmias and in untreated guinea pigs. The ischemic induced arrhythmias are aggravated by PAF in open-chest dogs. TX receptor antagonizing substances such as BM 13177 and specific PAF antagonists for example BN 52021 and WEB 2086, completely inhibited the PAF induced cardiac arrhythmias. An inhibitor of lipoxygenase such as esculetin inhibited the PAF effect to a small extent, too. Non-specific PAF antagonists such as diltiazem, diazepam, buphenin and trapidil have no or only a slight influence on PAF induced arrhythmias, although the antiarrhythmic effect of diltiazem and trapidil was shown on ouabain induced arrhythmias without PAF. The present study supports the hypothesis that PAF aggravates cardiac arrhythmias under pathophysiological conditions in which PAF is involved. Specific PAF antagonists and TX receptor antagonists induce antiarrhythmic effects under these conditions.

Aconitic Acid↗
PubMed1988

Correlations between endogenous prostaglandin E formation in the bone and spongiosa density.

The formation of prostaglandin (PG) E in the femoral head and the lumbar vertebral body of rats under ex vivo conditions after a linoleic acid (LA) rich diet (13.3 J%) has been compared to that of rats after an LA poor diet (0.5 J%). LA rich diet increased the formation of PGE in the lumbar vertebral body. In the femoral head were a similar, but statistically insignificant effect. The spongiosa density in the femoral head and the lumbar vertebral body increased after LA rich diet in contrast to LA poor fed rats. We conclude that the spongiosa density could be modulated by the LA content of the diet possible via alterations of endogenous PG biosynthesis.

Animals↗
PubMed1988

Influence of acetylsalicylic acid and BM 13177 on blood pressure and efficacy of antihypertensive drugs in spontaneously hypertensive rats.

The effects of the cyclooxygenase inhibitor acetylsalicylic acid (ASA) and of the TXA2 receptor antagonist BM 13177 on blood pressure and on the efficiency of antihypertensive drugs were investigated in spontaneously hypertensive rats (SHR). ASA and BM 13177 applicated once caused a significant, but short-lasting decrease in blood pressure in SHR. In contrast, repeated application of ASA (3 x 100 mg/kg) caused a slight, but significant increase in blood pressure. Pretreatment with BM 13177 (60 mg/kg i.v.) did not influence the antihypertensive effect of the drugs clonidine, propranolol and dihydralazine. Pretreatment of SHR with ASA intensified significantly the effect of these drugs on blood pressure, independent of their mode of action, and on heart rate (dihydralazine). The formation of TXB2 in the aorta thoracica in ASA pretreated SHR 20 min after drug application, was more strongly inhibited than was the formation of PGI2. Therefore the TXA2/PGI2 balance shifted in favor of the latter. However, in normotensive rats, ASA was without any effect on blood pressure and on the antihypertensive efficacy of the drugs. In conclusion it could be suggested that prostanoids are involved in the short term as well as in the long term regulation of the blood pressure and in the blood pressure lowering activity of drugs at least in a hypertensive state.

Animals↗
PubMed1987

The effect of the specific PAF antagonist BN 52021 and the calcium blocker diltiazem on PAF induced arrhythmogenicity.

Platelet-activating factor (PAF) in a concentration of 10(-11) mole per animal decreased the threshold doses for onsets of arrhythmia, ventricular flutters and fibrillation in ouabain induced arrhythmia in guinea-pigs in a statistically significant manner. The specific PAF antagonist BN 52021 (20 mg/kg, orally) completely inhibited the PAF effect for all types of arrhythmia, while the Ca2+ antagonistic drug diltiazem (0.1 mg/kg, i.v.) failed to counteract the PAF action. BN 52021 (20 mg/kg, per os) alone did not exert any effect on ouabain induced arrhythmia, but as expected, diltiazem (0.1 mg/kg, i.v.) showed antiarrhythmic effects. These results confirm the specific PAF antagonistic activity of BN 52021, its usefulness for PAF related cardiac rhythm disturbances and indicate that the method used could be a further useful tool to screen PAF antagonistic substances.

Administration, Oral↗
PubMed1987

The effect of PAF (platelet-activating factor) on experimental cardiac arrhythmias and its inhibition by substances influencing arachidonic acid metabolites.

Platelet-activating factor (PAF), 10(-11) mol decreased the threshold of ouabain induced arrhythmia in guinea-pigs. The thresholds inducing premature ventricular beats and ventricular flutter were statistically significantly decreased by 27.4% and 15.6%, respectively. BM 13.177 (30 mg/kg), a thromboxane receptor antagonizing substance, and esculetin (1.2 mg/kg), a lipoxygenase inhibitor, abolished this arrhythmogenic effect of PAF. Acetylsalicylic acid (10 mg/kg) showed only a tendency to inhibit the PAF effect. These results suggest that PAF could play a role in cardiac arrhythmias under special conditions and it supports the hypothesis that PAF action is mediated by the release of leukotrienes and thromboxane.

Animals↗
PubMed1987

Stimulation of aggregation and thromboxane A2 formation of human platelets by hypoxia.

The influence of hypoxia on the spontaneous platelet aggregation (SPA) and thromboxane formation was studied. The analysis of aggregation curve was carried out according to Breddin. The hypoxia enhanced the aggregability from Q2norm = 2.46 +/- 0.40 (normoxia) to Q2hyp = 4.39 +/- 0.39 (hypoxia), n = 52, p less than 0.001. 10 samples of those showed no SPA under equilibration with air but the hypoxic stimulus provoked SPA (Q2norm = 0, Q2hyp = 1.19 +/- 60, n = 10, p less than 0.001). When the results were arranged according to the degree of the stimulation of SPA, two groups could be separated with low and high response to hypoxia. The hypoxia caused also an augmentation of the TXB2 level in comparison to normoxia. The stronger enhancement of the TXB2 formation during the incubation under hypoxic conditions was independent of the fact whether SPA took place or not. The present study suggests that hypoxic conditions alone may be a reason for a stimulated TXA2 formation of the platelets and that the enhanced TXA2 formation caused by hypoxia is possibly inducing or reinforcing the SPA.

Adult↗
PubMed1987

Inhibition of thromboxane B2 formation of blood platelets by trapidil and other s-triazolo(1,5-a)pyrimidine derivatives.

Trapidil and some other 5,7-disubstituted s-triazolo(1,5-a)pyrimidine derivatives (TPDs) which were shown to have potent actions against platelet aggregation also inhibited in vitro platelet thromboxane A2 (TXA2) biosynthesis in clotting human and rabbit whole blood as well as in arachidonic acid-activated platelet-rich human plasma. The inhibitory potency of TPDs on TXB2 formation paralleled the antiaggregatory effectiveness to a certain extent and decreased in the following order: AR 12456 greater than AR 12463 approximately AR 12464 approximately AR 12465 greater than trapidil. When TPDs were administered orally to rabbits and blood was taken 2 hours later, no changes of serum TXB2 level were observed. After i.v. injection of TPDs in rabbits, the most active TPDs AR 12456 and AR 12463 led to a short-lasting reduction of serum TXB2 by 61.4 and 49.4% resp.. The TXB2 levels returned nearly to pre-treatment level after 80 min. The possibility is discussed that TPDs mainly prevent platelet TXA2 formation by inhibiting phosphodiesterase activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

Inhibition of thromboxane A2 production by trapidil and trapidil derivatives in the arachidonic acid-injected rat.

Trapidil and four selected 5,7-disubstituted s-triazolo (1,5-a)pyrimidine derivatives (AR 12456, AR 12463, AR 12464, AR 12465) which have already been shown to possess inhibitory effects on arachidonic acid(AA)-induced aggregation and thromboxane A2(TXA2) formation in human and rabbit platelets in vitro diminished the AA-stimulated TXA2 production in murine blood in vivo. The inhibitory effects of the derivatives were generally stronger than those of trapidil. The strongest inhibitor of TXA2 formation was the derivative AR 12456. These in vivo results correspond well with our previous in vitro findings.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

Do endogenous lipoproteins modulate the sensibility of animals against arrhythmogenic drugs?

The present study suggests that a diminished level of HDL is connected with an enhanced susceptibility to arrhythmogenic stimuli only in rats pretreated with a diet deficient in polyunsaturated fatty acids (PUFA), but not after a PUFA-rich or pellet diet. The endogenous level of total cholesterol did not influence the thresholds for ventricular flutter or ventricular fibrillation in aconitine-induced arrhythmia in rats or in ouabain-induced arrhythmia in guinea pigs.

Aconitine↗