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P V Avdonin

Publications and source records attributed to P V Avdonin.

At least 19 recordsLinked to original sources
PubMed2006

Disturbances in hormonal regulation of vascular tone during traumatic shock.

Changes in hormonal regulation of the vascular tone in Wistar rats were studied on Cannon model of traumatic shock. The pressor response to angiotensin II decreased by 30-40% 3 h after the incidence of trauma. The reaction to vasopressin remained unchanged. However, phenylephrine in medium and high doses produced a more pronounced pressor response under these conditions. One day after trauma we revealed a decrease in vascular sensitivity not only to angiotensin II, but also to vasopressin and alpha1-adrenoceptor agonist phenylephrine. The vascular response was observed only after treatment with phenylephrine in maximum doses. Traumatic shock was accompanied by inverse response to serotonin: hypertensive effect instead of blood pressure drop. Our results show that traumatic shock is accompanied by specific changes in vascular reactivity.

Angiotensin II↗
PubMed2006

[C677T mutation in methylentetrahydrofolatereductase gene in patients with venous thromboses from the central region of Russia correlates with a high risk of pulmonary artery thromboembolism].

AIM: To investigate genetic factors of risk (RF) to develop venous thrombosis and pulmonary artery thromboembolism (PATE) in population of central Russia. MATERIAL AND METHODS: We studied polymorphism of the genes of coagulation factor II (G20210A), factor V (G1691A) and methylentetrahydrofolatereductase (MTHFR) with polymerase chain reaction and restriction analysis of DNA amplified sites. We estimated prevalence of the mutations in healthy population and in patients with flebothrombosis as well as effects of the mutations on a PATE rate in patients with thrombosis. We examined 97 patients with documented flebothrombosis. PATE was detected in 54 of them. The control group consisted of 56 healthy volunteers matched by age and gender. RESULTS: G1691A mutation in the gene of coagulation factor V (Leiden mutation of factor V--LMFV) in healthy population occurred in 3.6%, in patients with flebothromboses--in 19.6% (OR = 6.58; 95% CI from 1.47 to 29.42; p = 0.006). Heterozygous mutation G20210A in prothrombine gene was detected in 8 (8.2%) patients (p = 0.027), while this mutation was registered in none controls. Polymorphism of MTHFR gene (C677T) was seen both in the control and patients (60.7 and 52.6%, respectively). LMFV occurrence in patients with flebothrombosis and PATE is less than in patients with flebothrombosis without TEPA (16.7 and 23%, respectively). The PATE risk is significantly higher in carriers of mutant allele 677CT and 677TT of MTHFR compared to patients free of this mutation (OR = 3.11; CI 95% from 1.35 to 7.15; p = 0.006). Homozygous inheritance of this mutation in males combined with PATE in 100% cases. Of 8 carriers of heterozygous mutation G20210A in prothrombin gene PATE was detected in 5 carriers. CONCLUSION: LMFV and mutation G20210A in prothrombin gene are genetic risk factors of venous thrombosis. LMFV is not a PATE risk factor. Mutation C677T in MTHFR gene has no influence on the risk of venous thromboses but makes PATE much more probable. This suggests that it may be a genetic risk factor of PATE in this disease.

Adolescent↗
PubMed2005

[Antiphospholipid syndrome in the structure of hematogenic thrombophilia in young and middle-aged patients with venous thrombosis].

AIM: To specify detectability and clinical presentation of antiphospholipid syndrome (APS) in young and middle aged patients with phlebothromboses (PT). MATERIAL AND METHODS: Enzyme immunoassays for lupus anticoagulant, PCR determination of G1691A mutation in the gene of coagulation factor V, mutation G20210A in prothrombin gene, mutation C677T in methylenetetrahydrofolate reductase (MTHFR) gene were made in 97 patients (57 males and 40 females) with venous thrombosis as well as estimation of external and internal coagulation, antithrombin III activity, protein C activity, plasma fibrinogen, stimulated platelet aggregation, blood and plasma viscosity. RESULTS: APS was detected in 20.6% young and middle-aged patients with venous thrombosis, in 18.5% of them--primary APS. In APS patients acquired risk factors of thrombosis occurred significantly less frequently than in patients with venous thrombosis free of APS (30 and 70%, respectively). Recurrent pulmonary artery thromboembolism (TEPA) prevailed in APS patients. In patients with combined hemostatic disturbances (APS+mutation) TEPA was diagnosed more frequently than in APS patients and in the absence of markers of genetic thrombophilia. Plasma viscosity is most important diagnostically among rheological indices.

Adolescent↗
PubMed2002

[Plasmapheresis in combine therapy of hypercoagulation syndrome in hematogenic thrombophilia].

AIM: To specify indications to plasmapheresis (PA) and to assess its efficiency in patients with hypercoagulatory syndrome in hematogenic thrombophilia (HT). MATERIAL AND METHODS: 18 patients (11 males, 7 females, age 26-50 years) with various forms of HT received standard antiaggregation, anticoagulatory therapy plus therapeutic PA. By PA technique the patients were divided into two groups. RESULTS: A positive trend in clinical, instrumental and laboratory indices was observed in all the patients. CONCLUSION: Therapeutic PA in hypercoagulation syndrome in HT patients leads to fast normalization of the clinical picture and reestablishment of patency of thrombus-affected vessels.

Adult↗
PubMed2001

Upregulation of vasopressin V1A receptor mRNA and protein in vascular smooth muscle cells following cyclosporin A treatment.

1. The major side effects of the immunosuppressive drug cyclosporin A (CsA) are hypertension and nephrotoxicity. It is likely that both are caused by local vasoconstriction. 2. We have shown previously that 20 h treatment of rat vascular smooth muscle cells (VSMC) with therapeutically relevant CsA concentrations increased the cellular response to [Arg8]vasopressin (AVP) by increasing about 2 fold the number of vasopressin receptors. 3. Displacement experiments using a specific antagonist of the vasopressin V1A receptor (V1AR) showed that the vasopressin binding sites present in VSMC were exclusively receptors of the V1A subtype. 4. Receptor internalization studies revealed that CsA (10(-6) M) did not significantly alter AVP receptor trafficking. 5. V1AR mRNA was increased by CsA, as measured by quantitative polymerase chain reaction. Time-course studies indicated that the increase in mRNA preceded cell surface expression of the receptor, as measured by hormone binding. 6. A direct effect of CsA on the V1AR promoter was investigated using VSMC transfected with a V1AR promoter-luciferase reporter construct. Surprisingly, CsA did not increase, but rather slightly reduced V1AR promoter activity. This effect was independent of the cyclophilin-calcineurin pathway. 7. Measurement of V1AR mRNA decay in the presence of the transcription inhibitor actinomycin D revealed that CsA increased the half-life of V1AR mRNA about 2 fold. 8. In conclusion, CsA increased the response of VSMC to AVP by upregulating V1AR expression through stabilization of its mRNA. This could be a key mechanism in enhanced vascular responsiveness induced by CsA, causing both hypertension and, via renal vasoconstriction, reduced glomerular filtration.

Animals↗
PubMed2000

Ca2+-agonistic effect of a T-type Ca-channel blocker mibefradil (Ro 40-5967).

Here we report that a Ca2+ antagonist mibefradil (Ro 40-5967) which has been shown to be a selective inhibitor of T-type calcium channels increases free calcium concentration ([Ca2+]i) in the cytoplasm of cultured smooth muscle cells isolated from porcine coronary artery. Smooth muscle cells were loaded with Fura 2 and a videoimage system was used to follow the [Ca2+]i responses. It was shown that at a concentration of 1 nM mibefradil induced a transient [Ca2+]i elevation in individual cells and at a concentration of 100 nM this compound stimulated almost all the cells in monolayer. The [Ca2+]i response did not change with the further increase of the mibefradil concentration up to 10 microM. The half-maximal effect was observed at 10 nM. The increase in [Ca2+]i strongly depended on the presence of Ca in the extracellular medium. Calcium antagonists belonging to three different classes--verapamil (phenylalkylamines), diltiazem (benzothiazepines) and amlodipin (dihydropyridines) neither suppressed the mibefradil effect nor mimicked it. These data indicate that mibefradil increased [Ca2+]i acting via a distinct receptor site. We suggest that these receptors are coupled to calcium channels of plasma membrane.

Amlodipine↗
PubMed2000

[Calcium antagonists nicardipine and verapamil suppress Ca(2+) entry and activate Na(+) entry into platelets].

In micromolar concentrations both antagonists suppressed CA2+ entry and simultaneously elevate the agonist-induced plasma membrane depolarization due to Na+ inward current via these channels. Potentiation by nicardipine of the Na+ current induced by the platelet-activating factor, was revealed. Both antagonists caused plasma membrane depolarization suppressed by Na+ and Ca2+ ions. The depolarization disappeared after substitution of NaCl by an isotonic solution of choline chloride. The antagonists nicardipine and verapamil seem to modulate the platelet receptor-operated channels suppressing Ca2+ entry and elevating Na+ current via these channels.

Benzofurans↗
PubMed1999

Cyclosporine A up-regulates angiotensin II receptors and calcium responses in human vascular smooth muscle cells.

BACKGROUND: The most widely used immunosuppressive drug for preventing graft rejection and treating autoimmune diseases is currently cyclosporine A (CsA). However, CsA also causes vasoconstriction, which is considered to be at the origin of CsA-induced nephrotoxicity and hypertension. To evaluate the cellular basis for these side effects, we studied the influence of CsA on the regulation of the free cytosolic Ca2+ concentration ([Ca2+]c) in cultured human vascular smooth muscle cells (SMCs). METHODS: SMCs were isolated from the medial layer of human aorta. [Ca2+]c regulation was studied by fluorimetry with fura 2 and by measuring 45Ca2+ effluxes. Angiotensin II (Ang II) receptors were detected by [125I]Ang II binding. RESULTS: Pretreatment of human SMCs for 24 hours with CsA in its therapeutic concentration range (0. 1 to 10.0 microM) had no effect on basal [Ca2+]c, but increased the [Ca2+]c elevation and 45Ca2+ efflux when cells were stimulated with Ang II. Half-maximal effects occurred at approximately 1 microM CsA. The CsA effects on [Ca2+]c were accompanied by a nearly twofold increase in Ang II receptor number, whereas no change in affinity to Ang II was observed. CsA did not alter endothelin-1- or thapsigargin-induced 45Ca2+ efflux. Increases in both Ca2+ responses and [125I]Ang II binding were attenuated by the transcriptional inhibitor actinomycin D. The effects of CsA did not appear to be mediated by calcineurin inhibition because cyclosporine H, which is not immunosuppressive, also increased the Ang II-induced 45Ca2+ efflux. CONCLUSION: These data suggest that CsA preferentially up-regulates the transcription of Ang II receptors, which very likely leads to vasoconstriction in vivo and could be at the origin of CsA-induced hypertension and nephrotoxicity in humans.

Angiotensin II↗
PubMed1994

Rat aortic smooth muscle cells expressing charybdotoxin-sensitive potassium channels exhibit enhanced proliferative responses.

1. The relationship between the expression of potassium (K+) channels and the growth properties of cultured vascular smooth muscle cells was examined. 2. Two groups of cells having different proliferative rates were cultured from the Wistar-Kyoto rat aorta. One group of cells, derived from early passages (3-5), proliferated with a cell doubling time of 2.41 days. A second group of cells, derived from late passages (> 12), proliferated at a higher rate (cell doubling time, 0.61 days). 3. Exposure of the early passaged cells to endothelin-1 (0.1 mumol/L) induced membrane depolarization. In contrast, exposure of the late passage cells to endothelin-1 (0.1 mumol/L) evoked a rapid hyperpolarization. The hyperpolarization in the late passage cells was blocked by charybdotoxin (20 nmol/L), an inhibitor of the large-conductance Calcium (Ca)-activated K+ channel. 4. The authors conclude that rapidly proliferating vascular smooth muscle cells express enhanced activity of Ca-activated K+ channels causing marked alterations in the electrical properties of the cells. It is therefore suggested that the reported increase in Ca-activated K+ channel activity in the aortae of hypertensive rats is likely to be associated with the increased proliferative ability of the vascular smooth muscle cells.

Animals↗
PubMed1994

Different electrical responses to vasoactive agonists in morphologically distinct smooth muscle cell types.

Vascular smooth muscle cells (SMCs) in the blood vessel wall are frequently heterogeneous in nature, differing in their gross morphology, size, and shape, subcellular organelles, cytoskeleton, and contractile protein composition. In adult rat arterial vessels, two populations of SMCs have been shown to predominate: elongated bipolar cells, representing the majority of cells, and epithelial-like SMCs. We examined the ionic responses of these two types of SMCs, isolated by multiple subculture, to vasoactive stimuli. Elevations in intracellular Na+ and Ca2+ were measured with SBFI and fura 2, respectively, and changes in membrane potential were measured using the potential-sensitive fluorescent probe bis-oxonol. The resting membrane potential of the elongated bipolar cells was less negative than that of the epithelial-like SMCs. Exposure of the elongated SMCs to endothelin 1, alpha-thrombin, or arginine vasopressin induced elevations in [Ca2+]i and [Na+]i and membrane depolarization. Depolarization occurred because of entry of both Na+ and Ca2+, and pharmacological blockade of Cl- or K+ channels did not attenuate the depolarization. In contrast, when [Ca2+]i was elevated by the same agonists in the epithelial-like SMCs there was a pronounced hyperpolarization that appeared to be the consequence of enhanced activity of charybdotoxin-sensitive Ca(2+)-activated K+ channels because it was abolished by charybdotoxin (20 nmol/L), partially attenuated by tetraethylammonium chloride (10 mmol/L), and unaffected by apamin (1 mumol/L), glibenclamide (1 mumol/L), or 4-aminopyridine (5 mmol/L). Chelation of [Ca2+]i also abolished the hyperpolarization; instead, a small depolarization was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Evidence for involvement of a GTP-binding protein in activation of Ca2+ influx by epidermal growth factor in A431 cells: effects of fluoride and bacterial toxins.

Aluminium fluoride (AlF4-), a G protein activator, was used to study a possible role of G protein in the control of the pathways for Ca2+ influx through plasma membrane of human carcinoma A431 cells. Fluorimetric measurements with the Ca2+ indicator Indo-1 have shown that addition of fluoride induces an increase in concentration of cytosolic free calcium ([Ca2+]in) due to both release of Ca2+ from intracellular stores and Ca2+ influx from the extracellular medium. The cells stimulated by fluoride became unresponsive to subsequent addition of epidermal growth factor (EGF), histamine and bradykinin. The Ca2+ signal induced by fluoride as well as one induced by EGF was inhibited by the pretreatment of cells with protein kinase C activator, phorbol myristate acetate (PMA). The pretreatment of the cells with pertussis toxin produced no effect on EGF-induced calcium response. In contrast, the pretreatment with cholera toxin (CTX) increased the basal level of [Ca2+]in and abolished the effect of EGF. The effects of CTX could not be reproduced by treating the cells with forskolin or IBMX, agents known to elevate cAMP content in the cell. Patch clamp experiments have shown that fluoride increases the activity of Ca(2+)-permeable channels identical to those activated by EGF from the extracellular side of the membrane [Mozhayeva et al. (1991) J. Membr. Biol. 124, 113-126]. The results obtained suggest the involvement of GTP-binding protein in signal transduction from the EGF receptor to Ca(2+)-permeable channel of plasma membrane in A431 cells.

Calcium↗
PubMed1992

[Increase of calcium-dependent activity of phospholipase C in the myocardium in adaptation of animals to short-term stress effects].

The effect of adaptation of rats to repeated short-term stress exposures was studied on the density and the affinity of alpha 1-adrenoceptors in the heart and on the phospholipase C activity and sensitivity to changes in Ca2+ concentration. It was found that adaptation to stress was accompanied by a desensitization of alpha 1-adrenoceptors and also by an increase in Ca(2+)-dependence of phospholipase C activity in the heart. The role of increased activity of phospholipase C and activated inositol triphosphate-diacylglycerol regulatory cascade is discussed as regard to the previously revealed accumulation of heat shock proteins in the myocardium and to the adaptive protection of the heart.

Adaptation, Physiological↗
PubMed1991

Stimulation of non-selective cation channels providing Ca2+ influx into platelets by platelet-activating factor and other aggregation inducers.

To elucidate the mechanism of the receptor-stimulated Ca2+ entry into human platelets, the influence of Ca(2+)-mobilizing agonists on plasma membrane potential (Em) has been studied. Em changes were registered using potentiometric probe 3,3'-dipropyl-2,2'-thiadicarbocyanine iodide. The agonist effect on Em varied from hyperpolarization to slight and slow rise. On the contrary, after loading of platelets with intracellular Ca2+ indicator quin2, platelet-activating factor (PAF), thrombin, vasopressin, ADP and thromboxane-A2-mimetic U46619 cause substantial transient membrane depolarization. Similar effects were observed after platelet loading with other Ca2+ chelators fura-2 and indo-1. Agonist-induced depolarization considerably reduced if quin2-loaded platelets were suspended in isoosmotic choline-containing medium. Using Ba2+ as a substitute of Ca2+, we have demonstrated that in choline-containing medium PAF-induced Ba2+ entry into platelets results in membrane depolarization. Dependence on Ba2+ concentration and depolarization kinetics correlates with the dose dependence and kinetics of Ba2+ entry detected by quin2 fluorescence. The agonists also stimulate considerable Na+, Li+ and Cs+ inward currents into platelets. Na(+)-dependent depolarization is 2-5-fold suppressed by extracellular Ca2+ [median inhibitory concentration (IC50) approximately 0.3 mM]. Ni2+ and Cd2+ at similar concentrations block Ca2+ entry and agonist-induced Na2+ current (IC50 for both cations approximately 50 microM). Agonist-induced depolarization is blocked by the adenylate cyclase stimulator prostaglandin E1 and the protein kinase C stimulator phorbol ester. It is concluded that agonists stimulate Ca2+ entry into human platelets via receptor-operated channels which are not strictly selective toward divalent cations and are permeable to Na+, Li+ and Cs+.

Aminoquinolines↗
PubMed1990

[Increase of calcium ion level in the cytoplasm of indo 1-loaded HeLa cells under the action of histamine].

The regulation of free cytoplasmic calcium in HeLa cells was studied using a fluorescent calcium indicator into 1. It is found that addition of histamine caused substantial increase in calcium level. In calcium-free medium the increase was much smaller, implicating both intra- and extracellular calcium as sources of observed Ca2(+)-rise. Protein kinase C activator, phorbol myristate acetate, completely blocked the effect of histamine. Agents causing rise in cellular cAMP level did not change the Ca2(+)-rise.

Calcium↗
PubMed1989

Phorbol ester stimulates platelet spreading and thrombi-like aggregate formation on the surface of immobilized type V collagen.

We have studied the effect of the tumor-promoting phorbol ester, 4 beta-phorbol-12 beta-myristate-13 a-acetate (PMA), and of the stable prostaglandin endoperoxide analogue U46619 on the interaction of human blood platelets with surfaces coated with monomeric human type V collagen (CV) and on free calcium concentration in platelet cytoplasm. It was shown by scanning electron microscopy that native resting platelets sparingly attach to CV and fail to spread or aggregate on the collagenous substrate in the absence of PMA and U46619. Addition of 0.15-1.5 nM PMA or 1.5 microM U46619 stimulates platelet spreading and formation of multilayer (thrombi-like) platelet aggregates on the per se non-thrombogenic type V collagen substrate. It was further demonstrated using the fluorescent indicator quin2 that U46619 (0.1 microM) increases cytoplasmic free calcium concentration from basal level (100-120 nM) up to 600 nM, whereas PMA (0.75-15 nM) exerts only a minor effect, increasing free calcium level by 30-40 nM. These results indicate that the tumor-promoting phorbol ester PMA induces massive platelet spreading and aggregation on surfaces coated with non-thrombogenic type V collagen via activation of protein kinase C with little or no apparent change in free cytoplasmic calcium.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1989

Selective inactivation by endogenous protein kinase C of human platelet high-affinity GTPase coupled with PAF receptors.

Incubation of human platelets with protein kinase C activator 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (PMA) abolished stimulation of membrane high-affinity GTPase by platelet-activating factor (PAF). GTPase stimulation by epinephrine decreased by 30%, while the prostaglandin E1 (PGE1) effect was unchanged. Basal GTPase activity (22.4 +/- 1.1 pmol Pi/min per mg protein) was not affected by PMA. Therefore, a study was performed of the effect of endogenous protein kinase C activation on adenylate cyclase regulation by agonists. PMA pretreatment completely suppressed PAF inhibition of basal adenylate cyclase activity but hardly influenced the inhibition by PAF of forskolin-stimulated activity. Adenylate cyclase inhibition by epinephrine in the presence of propranolol was not suppressed completely after platelet incubation with PMA. Epinephrine effects on basal and forskolin-stimulated activities decreased equally. Platelet pretreatment with PMA increased PGE1-stimulated activity by abolishing the inhibitory effect of high GTP concentrations. These studies indicate that protein kinase C selectively inhibits PAF effects, presumably by inactivating a GTP-binding protein coupled with PAF receptors.

Adenylyl Cyclases↗
PubMed1989

Dual-phase response of bovine pulmonary artery endothelial cells to agonists which increase free cytoplasmic calcium concentration.

The regulation of free cytoplasmic calcium concentration ([Ca2+]i) was studied in bovine pulmonary artery endothelial cells (BPAEC). The cells were seeded on the inner surface of glass cuvettes, grown to confluency and loaded with INDO-1. Using a multiwavelength method for estimation of [Ca2+]i it was shown that in Ca2+ containing medium a rapid rise of [Ca2+]i occurs in response to bradykinin, ATP or thrombin followed by a much slower decrease in free cytoplasmic calcium. Binding of extracellular Ca2+ by EGTA lowered basal [Ca2+]i but had no effect on the rate of agonist-induced [Ca2+]i increase or its absolute amount. In contrast, the kinetics of [Ca2+]i decrease were entirely different. A rapid (less than 0.5 min) decrease in [Ca2+]i to the basal level was observed immediately after the maximum had been achieved. If excess Ca2+ was added to the medium after EGTA, a second [Ca2+]i rise in response to the agonists occurred. The decrease in [Ca2+]i after the second peak was several times slower than the decrease in Ca2+ free medium. It is concluded that Ca2+ entry from the external medium had no effect on the maximal increase in [Ca2+]i but provides a severalfold increase in the duration the endothelial cell responses to the agonists.

Adenosine Triphosphate↗