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Biomedical subjects

O Petkov

Publications and source records attributed to O Petkov.

At least 19 recordsLinked to original sources
PubMed1996

Synthesis, gastroprotective, antisecretory and anti-Helicobacter effect of N-[3-(3-(1-piperidinylmethyl) phenoxy)propyl]-hydroxyacetamide 2-hydroxypropane-1,2,3-tricarboxylate bismuth (3+) complex (MX1)-MX1.

MX1 (N-[3-(3-(1-piperidinylmethyl)phenoxy)propyl]-hydroxyacetamide+ ++ 2-hydroxypropane-1,2,3-tricarboxylate bismuth (3+) complex) is a novel salt of the active metabolite of H2-antagonist roxatidine with a complex of bismuth with citric acid. In a model of ethanol-induced ulcers in male Wistar rats, both roxatidine and the bismuth salt reduced the number and the total length of lesions. Comparison of roxatidine and MX1 at equimolar doses of 160 mumol kg-1 showed a more potent cytoprotective effect of MX1. The potency of anti-secretory and antiacidic effects of MX1 was more than twice that of roxatidine on histamine-stimulated secretion in female Wistar pylorus-ligated rats. Microbiological tests with the reference bismuth preparation De-Nol showed prominent anti-Helicobacter properties of MX1 in-vitro. Both test compounds had similar range of MICs to Helicobacter pylori, from 4 to 64 microgram bismuth mL-1. The cytoprotective, antisecretory, anti-acidic and anti-Helicobacter properties of the new agent MX1 warrant further more extensive pharmacological and clinical trials.

Animals↗
PubMed1996

Computer design and syntheses of antiulcer compounds. 1st communication: N-[3-[3-(1-piperidinomethyl)phenoxy]propyl]amines and benzamides.

Aiming to develop new antiulcer agents, a quantitative structure-activity relationship (QSAR) study on in vitro (pA2) and in vivo histamine H2-receptor antagonistic activity of a series of N-[3-[3-(1-piperidinomethyl)phenoxy]propyl]amines was carried out using the OASIS computer system. The results showed that pA2 increases with the decrease (increase) of electron donor (acceptor) properties of molecules, particularly at the NH-reaction site. The finding is consistent with the assumption for an increase of histamine H2-receptor activity of the antagonists with their ability to form H-bonds with the receptor through NH groups. The correlations with hydrophobicity and related topological indices are consistent with the hypothesis that logP should indirectly reflect receptor interactions. In addition a series of N-[3-[3-(1-piperidinomethyl)phenoxy]propyl]benzamides are synthesized. The theoretically predicted in vitro activities of these compounds were found to be in accordance with in vivo tests (percent of inhibition of gastric juice and acid output [mEq/H+/3 h]).

Animals↗
PubMed1992

Interactions between the effects of endothelin-1, clonidine and yohimbine on electrically-induced contractions in rat vas deferens.

1. The relationship between endothelin-1(ET-1)-induced effects on the contractile responses of epididymal portion of rat vas deferens elicited by field electrical stimulation (FES: 80 V, 1 msec, 0.1 Hz) and the effects of the alpha 2-adrenoceptor agonist clonidine and the alpha 2-adrenoceptor antagonist yohimbine were studied. 2. ET-1 (0.01 nM-0.1 microM) concentration-dependently increased the FES-induced contractions. 3. ET-1 (0.1 nM-0.1 microM) reversed the inhibitory effect of clonidine on the FES-evoked contractions whereas ET-1 applied before clonidine exerted a dual effect on the clonidine-induced inhibition of the FES-evoked contractions. 4. The ET-1-induced enhancement of FES-induced contractions was potentiated in the presence of 1 microM yohimbine and was not observed at all in the presence of 10 microM yohimbine. Yohimbine, applied at concentrations of 1 and 10 microM exerted similar blocking effects on the alpha 1-adrenoceptor agonistic effects of phenylephrine. However, yohimbine at a concentration of 10 microM markedly potentiated the contractile effect of exogenous adenosine 5'-triphosphate (ATP), 30 microM. Tetrodotoxin abolished this effect of yohimbine. 5. The results presented here suggest the existence of modulating interactions between the ET-1-evoked increase of FES-induced contractions of rat vas deferens and the alpha 2-adrenoceptor drugs clonidine and yohimbine.

Adenosine Triphosphate↗
PubMed1991

Changes in the enzyme activity of the myocardium and participation of the alpha-adrenergic and M-cholinergic systems in experimental isoprenaline myocardial hypertrophy.

With a view to clarifying the mechanisms of haemodynamic stress, as well as the role of some neurotransmitter systems in the pathogenesis of myocardial hypertrophy (MH), a complex of experiments was carried out with an MH model induced in rats by isoprenaline treatment and by applying the M-cholinolytic agent atropine and the alpha-adrenergic blocker phentolamine in a part of the experimental groups. The changes in the activity of some enzymes of myocardial metabolism, namely: glucose-6-phosphate dehydrogenase, pyruvate kinase, alpha-hydroxy-butyrate dehydrogenase, isocitrate dehydrogenase, malate dehydrogenase and creatine phosphokinase, were traced in 33 male Wistar rats. Considerable activation of glucose-6-phosphate dehydrogenase was found in the different experimental groups, suggesting the adaptive "anti-stress" character of this change. The results of the pathobiochemical studies presuppose the substantial participation of the alpha-adrenergic and of the M-cholinergic systems in the stage of compensated isoprenaline-induced myocardial hypertrophy.

Animals↗
PubMed1990

[Action of the antihypertensive effect of captopril on manifestations of hypertrophy and several parameters of myocardial metabolism].

The administration of captopril (CP, 30 mg/kg) limited the arterial hypertension induced by the coarctation of the renal arteria and cardiac hypertrophy in rats. CP prevented the activation of MB-KK and glucoso-6-phosphate dehydrogenase. Besides CP decreased the activity of pyruvate kinase and increased that of malate dehydrogenase. These data demonstrate, that CP prevents both the cardiac hypertrophy and metabolic changes in animals with the renal hypertension.

Animals↗
PubMed1988

Preventive effect of captopril on the development of experimental hypertension in rats.

The arterial blood pressure (BP), the ratio between gram myocardial mass per 100 g body mass (R), the plasma renin activity (PRA) and the aldosteron content in the blood plasma (PA) were investigated in a model of renal hypertension, 30 days after the operation, in the following groups of male Wistar rats: operated and treated throughout the entire experimental period with captopril Pharmachim in a dose of 30 mg/kg body mass twice daily orally, and two control groups--operated and treated with saline, and non-operated animals of the same age, treated only with saline. BP, R and PA increase significantly in the control group with experimental hypertension. In the group treated with captopril PRA was more than doubled compared with the two control groups, with a considerable decrease in PA compared with the control group with hypertension. The results obtained for the captopril-treated experimental group (with the exception of PRA) are identical and close to the data for the control non-operated animals, i.e. the treatment of the experimental animals with captopril prevents the development of arterial hypertension and of myocardial hypertrophy with the coarctation hypertension model used.

Aldosterone↗
PubMed1985

Changes in blood plasma and myocardial lipids in experimental thyrotoxic myocardial hypertrophy in rabbits.

Blood plasma and myocardial total lipids (TL), cholesterol (Ch), triglycerides (TGL), phospholipids (PhL), as well as plasma free fatty acids (FFA) were studied in 56 male rabbits with experimental thyrotoxic myocardial hypertrophy, induced by Thyreotom (group T14-14 days, T45-45 days). Combinations with Trasicor (TT-14 days) and aminooxyacetic acid (TAOAA-14 days) were also applied. The data showed a significantly lower plasma Ch and TL levels both in T14 and T45 as compared to the control group. The myocardial levels of TGL both in T14 and T45 were significantly higher than in the control group. In the TT group, myocardial Ch tended to decrease. A considerable decrease in plasma and myocardial lipids was found in the TAOAA group. Treatment with Thyreotom with or without Trasicor or AOAA resulted in a decrease of polyunsaturated FA, which was most expressed in the TT group. The combinations with Trasicor and AOAA had a protective effect on thyrotoxic disturbances.

Aminooxyacetic Acid↗
PubMed1984

[Prevention of adrenaline-induced heart damage using the antioxidant ionol].

Experiments on an isolated papillary muscle of the rat heart left ventricle have demonstrated that pretreatment with the antioxidant ionol prevents the disturbances of myocardial contractility caused by administration of a large dose of adrenaline. The data obtained are in agreement with the concept that the prophylactic action of antioxidants during stress is determined by the fact that they prevent activation of lipid peroxidation in the heart under the action of excess catecholamines.

Animals↗
PubMed1983

Some functional changes in experimentally induced cardiac overload.

In connection with the elucidation of the mechanisms of the acute and chronic haemodynamic stress during cardiac overloading, as well as in investigations on the role of neurotransmitter systems in the genesis of myocardial hypertrophy (MH), we carried out a complex of studies involving modelling of MH induced by treatment of rats with isoprenaline (ISO.) and of rabbits with thyreotom (Tri-iodothyronin +L-Thyroxin). With a view to studying some pathogenetic factors participating in the characteristics of the reproduced pathological states, combinations with oxprenolol, atropine, phentolamine (Phent.) and amino-oxyacetic acid (AOAA), which is a GABA-inhibitor, were also applied. The results of the ECG studies performed are the main object of the present article. Marked MH was found in rats injected for 12 days with Iso. in doses of 2 mg/kg, as well as in rabbits which received thyreotom (accompanied with development of arterial hypertension). Considerable functional and morphological damage (with subendocardial fibrous proliferations) were discovered in rats treated with Iso. +Phent. The combinations of oxprenolol and AOAA manifested a protective effect to rabbits with thyrotoxic disturbances. Evident is also the essential role played by the adrenergic mechanisms in MH pathogenesis.

Aminooxyacetic Acid↗
PubMed1983

Study of the Adrenergic reactivity of the anococcygeal muscle in spontaneously hypertensive rats.

The experiments in the present work, representing a part of a wider study of the reactivity of smooth muscles of spontaneously hypertensive rats, were carried out on anococcygeal muscles of Wistar male and female normotensive rats (NTR) and on spontaneously hypertensive rats (SHR), divided in two age groups: young -2.5 to 4 months, and adult -6 to 12 months. The effects of noradrenaline (NA), isoprenaline (IPNA) and phentolamine (Ph) were studied in parallel experiments on smooth-muscle preparations of NTR and SHR. NA (1 x 10(-10)-1 x 10(-4) M) and IPNA (1 x 10(-4)) caused stronger contractions in NTR preparations. The affinity of alpha-adrenoreceptors to NA was increased in the SHR preparations. Ph (1 x 10(-8)-1 x 10(-6) M) inhibited more markedly the NA-contractile effects on smooth muscles of young male SHR. The inhibitory action of Ph On IPNA-induced contractions was less manifested on SHR anococcygeal muscles. It is seen from the results obtained that the adrenergic reactivity of SHR anococcygeal muscle is reduced, which is in agreement with the data in the literature and with our earlier assumption concerning the mosaic character of the specific features of the adrenergic transmission in SHR. The established increased affinity to the transmitter of the alpha-adrenergic receptors in SHR probably represents a peculiar compensatory mechanism for facilitating the adrenergic neurotransmission with reduced capacity of the smooth-muscle effector system to transform the stimulus generated during contraction.

Age Factors↗
PubMed1981

Content of prostaglandins E and F in the blood plasma and kidneys in arterial hypertension (clinical-experimental study).

A dynamic study is made of the content of PGE and PGF2 alpha in the kidneys of rats with experimental coarctation hypertension, as well as the PGF2 alpha-metabolite in the blood plasma of the same experimental model in rats and in patients with arterial hypertension. The level of the PGF2 alpha-metabolite tends to decrease both in the animals with experimental hypertension and in hypertonic patients. In rats with 30-day hypertension low values are established in 55 per cent, while in 45 per cent there are high values of the PGE level in the kidney homogenate compared with the control group. The concentration of PGF2 alpha in the left ("endocrine") kidney (whose artery originates distally from the place of aortic coarctation) is higher than the concentration of the same PG in the right kidney. Our findings give grounds for the following assumptions: 1. The PGF2 alpha-metabolite as hormone and partly PGE in the kidneys seem to be involved in the pathogenesis of arterial hypertension as compensatory factors. 2. PGF2 alpha in the kidneys probably participates directly as one of the elements of the complex pathogenesis of arterial hypertension.

Adolescent↗
PubMed1978

The character of the antagonism by polyphloretin phosphate of contractions to prostaglandins E1 and F 2alpha in guinea-pig ileum.

Polyphloretin phosphate (PPP) produced a dose-dependent decrease in the tone and reduction of the spontaneous phasic contactions of the longitudinal muscle of guinea-pig isolated ileum. PPP (100 microgram ml-1) after a 2 min contact with the ileum decreased the contractile effects of PGE1 0.1 micron by 40.6 +/- 7.4%, of PGE1 0.01 micron by 86.7 +/- 3.3% and of PGE2alpha 0.1 micron by 62.2 +/- 8.6%. After 10 min contact of PPP the contractile effect of PGE1 0.1 micron was decreased by 47.7 +/- 4.7% and that of PGE2alpha 0.1 micron by 89.6 +/- 1.7%. When the contact was longer, PPP showed a pronounced after-effect in respect to the effects of PGE1 and particularly of PGF2alpha. PPP signicantly reduced contractions to 5-HT and BaCL2, but not to acetylcholine, histamine or substance P. The type of antagonism of PGE1 by PPP was examined using cumulative concentration-effect curves for PGE1 in the presence of increasing concentrations of PPP. We conclude that on guinea-pig ileum PPP acts as a non-competitive antagonist of PGE1 and PGF2alpha.

Acetylcholine↗
PubMed1978

Role of calcium in the mechanism of action of the prostaglandins E1 and F2 alpha as well as of their antagonist polyphloretin phosphate (PPP).

The contractile effect of PGE1 on guinea-pig ileum is not changed either by increase (to 4 mM) or by decrease (to 1 mM) of the Ca++ content in Krebs solution. The decrease of Ca++ in the medium intensifies the contractile effect of PGE2 alpha. Reduction of Ca++ weakens the antagonistic effect of PPP (100 micrograms/ml) against PGF2 alpha. PPP has a marked aftereffect with respect to the effects of PGF2 alpha--in cases of normal Ca++ content in the Krebs solution this aftereffect appears upon longer (10 min) contact of PPP with the intestinal segment, while in cases of changed Ca++ content it appears already after 2-min PPP action. It is concluded that in order to induce contractions in the guinea-pig ileum, PGE1 and PGF2 alpha utilize the internal Ca++. It is assumed that PGF2 alpha increases the reactivity of the anionic sites of the smooth-muscle membrane for Ca++. As a result of this, the complex compounds of Ca++ at its higher concentration make more difficult the realization of the contractile process. It is assumed that Ca++ is needed for the maximum manifestation of the antagonistic effect of PPP.

Animals↗