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Biomedical subjects

B Malomvölgyi

Publications and source records attributed to B Malomvölgyi.

At least 19 recordsLinked to original sources
PubMed1996

Comparison of the vasodilatory effects of bradykinin in isolated dog renal arteries and in buffer-perfused dog kidneys.

This study was undertaken to investigate the role of nitric oxide (NO), cyclooxygenase products and bradykinin (Bk) receptors in the Bk evoked responses of canine renal arteries and perfused kidneys. Rings of isolated canine renal arteries were mounted in organ chambers for measurement of isometric force. The isolated canine kidneys were perfused with Krebs-solution (constant flow) and the perfusion pressure was continuously recorded. The influence of the cyclooxygenase inhibitor indomethacin and the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginin (L-NOARG) on the vasocontractile responses to phenylephrine (PE) were examined in both preparations. Furthermore, the effects of Bk on the tone of canine isolated renal arteries and on the vasopressor responses of isolated buffer-perfused kidneys of dogs were tested in the absence and presence of enzyme inhibitors and the B2 kinin receptor antagonist HOE-140. It was found that indomethacin enhanced the contractile responses of large renal arteries to PE by 77 +/- 10%. In intact artery rings L-NOARG (0.1 mM) caused an additional potentiation of the PE-induced contractions in the presence of indomethacin (from 11.5 +/- 1.2 mN to 21.6 +/- 1.7 mN). However, L-NOARG failed to affect contractile responses to PE in endothelium-denuded rings. Bk produced a concentration-dependent relaxation of the precontracted endothelium-intact renal arteries. The IC50 value for Bk was 11.2 +/- 3.7 nM. The relaxant activity of the peptide in renal artery rings was not affected by indomethacin (3 microM). However, in the presence of L-NOARG a significantly higher concentration (IC50 = 860 +/- 300 nM) of Bk was required to relax renal arteries. The Bk receptor antagonist HOE-140 (10 nM for 40 min) attenuated the relaxant effect of Bk in renal artery rings (from an IC50 of 14.2 +/- 2.5 nM to 216 +/- 37 nM). Indomethacin (3 microM for 20 min) did not significantly alter the arteriolar vasoconstriction (from 45 +/- 4 mm Hg to 48 +/- 5 mm Hg, n = 5) evoked by PE. By contrast, L-NOARG (0.1 mM) potentiated (from 56 +/- 7 mm Hg to 94 +/- 11 mm Hg) the PE-induced vasopressor responses in perfused kidneys. Bk reduced the size of the pressor responses at relatively low concentrations (2-60 nM) but the dose-response curve was flat and the maximum inhibitory effect hardly exceeded 50 percent. Indomethacin (3 microM) did not modify the inhibitory effect of Bk in perfused kidney. In the presence of L-NOARG, Bk depressed the PE induced vasopressor effects with a maximum of 18 +/- 20%. Preincubation of the kidney preparations with the Bk antagonist HOE 140 (10 nM for 40 min) almost completely abolished the inhibitory effect of Bk on the PE induced vasopressor responses. The results suggest that the endothelial NO plays a fundamental role in the relaxant effect of Bk and considerably modulates vascular reactivity to PE in canine renal vasculature. Furthermore, significant difference exists between conduit and resistance vessels of dog's kidney in the effect of indomethacin on the adrenergic contractions.

Adrenergic beta-Antagonists↗
PubMed1991

Comparison of serotonin agonistic and antagonistic activities of a new antidepressant agent Trelibet (EGYT-475) and its metabolite EGYT-2760 on isolated rat fundus.

The effects of Trelibet (EGYT-475, N-benzyl-piperazine-picolinyl-fumarate) and its active metabolite (EGYT-2760, N-benzyl-piperazine) on the serotoninergic responses of rat stomach fundus were investigated and compared with those of MCPP (m-chlorophenyl-piperazine) which is the common metabolite of the arylpiperazine antidepressants Trazodone and Etoperidone. The contraction inhibitory potencies of the agents were determined on the equipotent contractions (EC50) to serotonin (5-HT) and prostaglandin F2 alpha (PGF2 alpha). Isotonic contractile responses to 5-HT were not affected by EGYT-475, however, both EGYT-2760 and MCPP produced concentration related and reversible inhibition of the serotoninergic responses. The IC50 values for EGYT-2760 and MCPP were 40.5 +/- 7.5 mumol/l and 125 +/- 35 nmol/l, respectively. The inhibition was selective for the serotoninergic responses, as the equipotent responses to PGF2 alpha were not affected. EGYT-2760 and MCPP displayed not only 5-HT antagonistic, but also partial agonistic activities on the rat fundus preparation. Maximum contractile response of the fundus preparation to MCPP was approximately 25%, to EGYT-2760 was 10% of the maximum response to 5-HT.

Animals↗
PubMed1988

Effects of PGI2, CH-7284 and CH-7384 on spontaneous platelet aggregation and blood pressure of anaesthetized beagles.

Chinoin-7284 and Chinoin-7384 are chemically stable derivatives of prostacyclin. We compared the hypotensive and antiaggregatory effects of PGI2 and the two analogues using our computerized aggregometric system. The in vivo antiaggregatory activity was measured with a modified filtration pressure technique in anaesthetized beagle dogs: The change in arterial blood pressure was measured simultaneously. The dose-response relationship and the duration of action of prostacyclin and their analogues following bolus administration have been determined. The molar dose of PGI2, CH-7284 and CH-7384 that produced 25 mmHg reduction in filtration pressure were 0.3 +/- 0.06 nmol/kg; 7.37 +/- 0.94 nmol/kg; 17.19 +/- 1.76 nmol/kg respectively (n = 6). The molar doses that produced the same decrease in mean arterial pressure were 0.61 +/- 0.06 nmol/kg; 15.59 +/- 4.73 nmol/kg; 21.05 +/- 7.20 nmol/kg respectively (n = 6). There were no significant differences between equipotent doses of prostacyclin and its analogues with respect to the duration of antiaggregatory and hypotensive action. The in vivo selectivity ratios (hypotensive potency/antiaggregatory potency) of PGI2, CH-7284 and CH-7384 were 0.49, 0.47 and 0.85 respectively. The results indicate that these two PGI2 analogues have the same character as regards the in vivo duration of actions and in vivo selectivity, as has the parent compound.

Animals↗
PubMed1988

In vivo antiaggregatory effect of BM 13.177 on the spontaneous platelet aggregation in anaesthetized beagle dogs.

The arterial blood of anaesthetized heparin-treated beagle dogs was directed through a 30/um diameter pore size screen by a roller pump at a constant rate. As a result, the pressure proximal to the filter continuously increased. The filtration pressure stabilizing concentration of prostacyclin (infused proximal to the filter) was determined. BM 13.177 -similar to PGI2- was able to slow down and stop the increase of filtration pressure (final conc.: 1-10/uM). In addition it could reverse the filter occlusion process. The lowest concentration of BM 13.177 (0.1-1/uM) did not affect significantly the filter occlusion rate, but it markedly enhanced the antiaggregatory effect of PGI2 when these drugs were administered simultaneously. In summary, we can conclude that 1) generation of thromboxane and endoperoxide plays a key role in the mechanism of the spontaneous platelet aggregation on the filter; 2) BM 13.177 significantly potentiates the antiaggregatory effect of PGI2 in vivo.

Animals↗
PubMed1988

Relaxation by prostacyclin (PGI2) of human, dog and rabbit femoral artery strips. Interspecies difference.

Helically cut femoral artery strips from humans (bypass surgery), dogs and rabbit were set up for isometric recording. The endothelial layer was removed by rubbing, hence the vascular strips used in this study are considered to be arterial smooth muscle preparations without endothelium. The indomethacin-, prostaglandin F2 alpha- and PGI2-induced changes in tone were determined. Indomethacin (3/mumol/l) potentiated the contractile responses of human and canine vessels to PGF2 alpha by 60.0 +/- 10.4 and 108 +/- 12%, respectively. By contrast, the PGF2 alpha-induced contractions of rabbit arteries were not enhanced by the cyclooxygenase inhibitor. PGI2 diminished the tone of the PGF2 alpha-contracted vessels obtained from all the three species in a concentration-related manner. The potency of the relaxant prostanoid differed, however, markedly (p less than 0.02) from species to species. The IC50 values (molar concentrations of PGI2 producing 50 percent reduction in the PGF2 alpha-induced tone) were 20.8 +/- 1.9, 133 +/- 24 and 286 +/- 52 nmol/l for human, dog and rabbit arteries, respectively. The results clearly demonstrate a significant interspecies difference in the prostacyclin-sensitivity of the blood vessels studied. The differential responsiveness to indomethacin may reflect species-difference in the regulatory function of PGI2 in arterial smooth muscle tone.

Animals↗
PubMed1988

Actions of PGE2 and indomethacin on adrenergic neuroeffector transmission in the rabbit coeliac artery.

In the present study we have investigated the pre- and post-synaptic actions of PGE2 and indomethacin on the adrenergic transmission in isolated coeliac arteries of rabbits. The artery segment was preloaded with (3H)NA and suspended in an organ bath (37 degrees C, 5% CO2 - 95% O2, isometric recording). The preparation was superfused with Krebs-solution containing the uptake blockers cocaine and corticosterone. To release neurotransmitter, the artery was stimulated by electrical square-wave pulses (0.5 ms, 5 Hz, 60 s) using platinum wire electrodes. The perfusate was collected in 3 or 6 min samples. The outflow of labelled neurotransmitter was expressed in pmol/3 min. Inhibition of endogenous prostaglandin-biosynthesis by indomethacin (3/mumol/l) potentiated the contractile responses to nerve stimulation (57 +/- 15%, n = 4), but did not influence the release of NA (the release ratio was 1.02 +/- 0.03, n = 4). The endogenous prostaglandins may modulate vascular neuroeffector transmission postjunctionally, because cyclooxygenase inhibition did not cause any change in transmitter release. The effects of exogenous PGE2 on adrenergic transmission and contraction were also studied. In this case, indomethacin was present to minimize the potential complicating actions of endogenous prostanoids. At low concentrations (1, 3 and 10 nmol/l) PGE2 dose-dependently inhibited vasoconstrictor responses to nerve stimulation (IC50 = 4.7 +/- 1.5 nmol/l, n = 4), but was ineffective in influencing transmitter release (the stimulation evoked release ratios were 0.95 +/- 0.05, 1.00 +/- 0.00 and 0.93 +/- 0.11, n = 4, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Species dependent relaxation of intrapulmonary arteries (IPA) of rabbits, dogs and humans by prostacyclin.

Helically cut strips of successive IPA segments of rabbits, dogs and human patients were set up for isometric recording in vitro. High tone was produced by norepinephrine (NE, 3 microM). This tone was markedly reduced by prostacyclin (PGI2) in the secondary, tertiary and quaternary branches of human and canine pulmonary trunk. The IC50 values for PGI2 ranged from 22 to 503 nM, the human vessels being more sensitive to prostacyclin than canine IPA. Under these conditions, the primary and secondary branches of the rabbit pulmonary trunk were not relaxed by PGI2. The contractile potency of NE was determined in each pulmonary vessel studied. The secondary segments of rabbit IPA were about ten times as sensitive to NE (EC50 for NE: 38 +/- 7 nM) as compared to the secondary IPA from dogs and humans (EC50 values: 370 +/- 84 and 440 +/- 50, respectively). When high tone was induced by equieffective contractile concentrations of NE (3 microM for canine and human IPA and 0.3 microM for rabbit vessels), PGI2 was still less effective (P less than 0.01) in relaxing secondary IPA of rabbits (IC25: 220 +/- 55) than the corresponding segments of dogs and humans (IC25: 51 +/- 12 and 17 +/- 4, respectively). The difference between canine and human vessels was also significant (P less than 0.02). These results indicate that there is an interspecies difference in the sensitivity of IPA to NE and PGI2.

Animals↗
PubMed1984

Differential contractile responsiveness of isolated rabbit arteries from different vascular beds to cyclooxygenase inhibitors and PGI2.

The actions of three, structurally unrelated cyclooxygenase inhibitors and PGI2 on the contractile responses to electrical stimulation and to noradrenaline of strips of rabbit coeliac, ear, pulmonary, carotid, femoral arteries and the aorta were studied. Indomethacin (3 mumol/l), suprofen (0.8 mumol/l) and meclofenamic acid (0.2 mumol/l) potentiated the adrenergically induced contractions of coeliac arteries by 126-165%. The contractile responses of ear arteries were increased by these three substances by 87-91%, and the responses of pulmonary arteries by 26-33%. All of these changes were statistically significant. Prostacyclin produced a dose-related inhibition of the stimulation-induced contractions of the coeliac, ear and pulmonary arteries; its IC50 values were 10.4, 212 and 433 nmol/l, respectively. In contrast to effects in the above arteries, the evoked contractions of aortic and carotid strips were not affected by any of the prostaglandin synthesis inhibitors used; the responses of femoral vessels were reduced by all of the inhibitors (by 13-23%; P less than 0.05). Low concentrations of PGI2 did not affect the evoked contractions of aortic, carotid and femoral strips whereas higher concentrations increased baseline tone and potentiated contractions. The results indicate that there are considerable difference in the sensitivities of the arteries from different vascular beds to inhibitors of cyclooxygenase and to prostacyclin.

Animals↗
PubMed1984

Effects of cyclooxygenase inhibitors, prostaglandins F2 alpha and I2, on isolated coeliac and basilar arteries of alloxan-diabetic dogs.

The effects of prostaglandin synthetase inhibitors PGF2 alpha and PGI2 on the tone of isolated basilar and coeliac arteries were studied in healthy and alloxan-diabetic dogs. PGF2 alpha (1 mumol 1-1) produced a significantly higher tone in diabetic basilar arteries (1.15 +/- 0.16 mN) than in normal cerebral vessels (0.7 +/- 0.10 mN). By contrast, the contractile responses of normal and diabetic coeliac arteries to PGF2 alpha did not differ. The cyclooxygenase inhibitors indomethacin (3 mumol 1-1) and suprofen (0.58 mumol 1-1) potentiated the PGF2 alpha-evoked contractions in all of the vessels studied. The percent potentiation was greater (50-60%) in the basilar arteries from alloxan-treated dogs than in normal basilar vessels (22-30%). There was not such a difference between diabetic and normal coeliac arteries. Prostacyclin produced a concentration-related relaxation in the presence of indomethacin or indomethacin + PGF2 alpha. The relaxant potencies of PGI2 were similar in the vessels from metabolically healthy and diabetic dogs. The IC50 values for PGI2 were 11.6 +/- 1.3 and 11.8 +/- 1.8 nmol 1-1 in normal and diabetic basilar arteries, respectively; they were 25.4 +/- 3.2 and 26.2 +/- 3.9 nmol 1-1 in control and alloxan-treated coeliac vessels. These results indicate that normal and diabetic vessels may have differential reactivity to cyclooxygenase inhibitors, this difference being dependent on the vascular region.

Animals↗
PubMed1984

Effects of cyclooxygenase inhibitors and PGI2 on the adrenergic contractions of isolated rabbit arteries.

The effect of three cyclooxygenase inhibitors (indomethacin, suprofen, meclofenamic acid) and PGI2 on the contractile responses to noradrenaline (NA) and to nerve stimulation (TNS) of strips of rabbit coeliac-, pulmonary-, ear-, carotid-, femoral arteries and the aorta were studied. The equipotent concentration (0.1 X EC50) of NA were calculated from dose-response curves. The stimulation parameters (Hz, duration) varied according to the responsiveness of the tissue. Both NA and TNS caused 7-23% of maximum response. In the presence of cyclooxygenase inhibitors (COI's) NA and TNS produced significantly greater proportion (15-30%) of maximum contraction in coeliac-, ear-, and pulmonary arteries. Contractions of the other 3 vessels were not influenced by COI's. The inhibitory potency of PGI2 was determined on contractions produced by equipotent concentration (EC50) of NA. PGI2 was highly effective in coeliac arteries, it was less potent in pulmonary- and ear arteries and had no effect on the responses of the other vessels.

Animals↗
PubMed1983

Effects of indomethacin and prostaglandins I2 and E2 on the tone of human isolated mesenteric arteries.

The actions of indomethacin (IND), PGE2 and PGI2 were studied on the tone of isolated mesenteric arteries obtained from operated patients. The cyclooxygenase inhibitors IND (3 mumol/l) and suprofen (0.58 mumol/l) increased the resting tone and potentiated the contractile responses to electrical stimulation and noradrenaline. Low concentrations of PGE2 (0.7-5.6 X 10(-9) mol/l) decreased the baseline tone and reduced the stimulation-evoked contractions whereas higher concentrations (from 5.7 X 10(-8) mol/l) increased the tone of vessels. PGI2 (0.7-10.8 X 10(-9) mol/l) also relaxed IND-treated arteries but, in contrast to PGE2, it did not produce contraction even at a concentration of 10(-6) mol/l. Prostacyclin reduced the tone evoked and sustained by a high concentration of PGE2 or PGF2 alpha, the IC50 values being 46.2 or 7.9 X 10(-9) mol/l, respectively. The contractile responses to electrical stimulation and to noradrenaline were also inhibited by PGI2 (IC50 5.6 and 6.8 X 10(-9) mol/l, respectively). These results suggest that the smooth muscle cells of human mesenteric arteries are just as sensitive to IND, PGE2 and PGI2 as are those from laboratory animals. Our observations may be of clinical importance.

Adult↗
PubMed1982

Nanomolar concentrations of prostaglandin F2 alpha potentiate cholinergic contractions of rabbit isolated tracheal muscle.

The effects of prostaglandin F2 alpha (PGF2 alpha) on stimulation- or acetylcholine-evoked contractions were studied in isolated airway muscle preparations from rabbits, guinea-pigs and humans. Low concentrations of PGF2 alpha (10(-9) to 9 X 10(-8) mol/1) produced a dose-related (10-300%) increase in the contractile responses of the rabbit trachealis muscle to electrical stimulation at 2 Hz. This effect was inversely related to the rate of stimulation. In seven out of forty two preparations the resting muscle tone was also increased by 1.1 X 10(-8) mol/1 or higher concentrations of PGF2 alpha. This substance enhanced the contractile responses to acetylcholine (1-2.7 X 10(-8) mol/1) to the same extent as those to electrical stimulation. The potentiation produced by PGF2 alpha was not affected by indomethacin, mepyramine, methysergide or phenoxybenzamine. Electrically evoked contractions of isolated tracheal strips of guinea-pig or segments of human bronchial muscles were not changed significantly in the presence of 0.1-5 X 10(-8) mol/1 of PGF2 alpha. These results suggest that PGF2 alpha may modulate airway muscle tone by enhancing the postsynaptic stimulatory effect of acetylcholine released from the pulmonary cholinergic nerve endings. This modulation seems to be species-dependent.

Acetylcholine↗
PubMed1982

Relaxation by prostacyclin (PGI2) and 7-oxo-PGI2 of isolated cerebral, coronary and mesenteric arteries.

The relaxant effects of prostacyclin (PGI2) and its stable 7-oxo-analogue, a product of Chinoin Pharmaceutical Works, were compared on isolated canine cerebral, bovine coronary, rabbit coeliac and human mesenteric arterial strips. The resting tone of the coronary, cerebral and human mesenteric arteries as well as the stimulation- or noradrenaline-evoked tone of coeliac vessels were reduced by both prostanoids. The relaxant action of 7-oxo-PGI2 was slow in onset and lasted until it was washed out. The IC50 values were 4 to 40 X 10(-9) mol/l for PGI2 and 1 to 6 X 10(-7) mol/L for 7-oxo-PGI2. Compared to PGI2, 7-oxo-PGI2 was more potent in relaxing coronary arteries than the other vessels studied. Isolated tracheae from guinea-pigs were contracted by PGI2 while relaxed by 7-oxo-PGI2.

Animals↗
PubMed1982

Effects of prostaglandins E2, I2 and F2 alpha on the tone of isolated coronary arteries from alloxan-diabetic dogs.

Contractile responses to PGF2 alpha of isolated coronary arteries from 7 healthy and 12 alloxan-diabetic dogs without ketosis were considerably increased by indomethacin and decreased by PGI2. The increasing effect of indomethacin was more prominent on diabetic vessels than on those of normal animals while PGI2 had the same relaxant potency in both groups. The contractions induced by PGF2 alpha were inhibited more effectively by PGI2 than those evoked by PGE2 both in healthy and alloxan-diabetic groups.

Animals↗
PubMedDate not supplied

Studies on the biochemical mode of action of EGYT-475, a new antidepressant.

We studied the mode of action of N-benzyl-piperazine-picolinylfumarate (EGYT-475) and of its metabolite N-benzyl-piperazine (EGYT-2760) in CFY rats. It was found that EGYT-475 had no uptake-inhibitory effect but EGYT-2760 inhibited the high-affinity uptake of 3H-noradrenaline, 3H-dopamine and especially that of 3H-serotonin both in vitro and ex vivo. Neither of the two compounds changed the serotonin turnover. Only EGYT-2760 evoked hyperthermia in rats at a high ambient temperature (28 degrees C). This effect was abolished by cyproheptadine but not by amitriptyline. EGYT-2760 antagonized serotonin-induced contractions of the stomach fundus but it was inactive in inhibiting the serotonin-induced platelet aggregation. Our results suggest that EGYT-2760, an active metabolite of EGYT-475, has a central serotoninomimetic action which involves 5-HT uptake-inhibition and 5-HT1 receptor agonistic effect.

Animals↗