Wyniki wyszukiwania

1

Anti-aggregatory prostanoids. Part II

100%

Korbut R., Gryglewski R. J.

Acta Physiologica Polonica

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1985

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tom 36

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nr 5-6

2

Anti-aggregatory prostanoids. Part I

100%

Korbut R., Gryglewski R. J.

Acta Physiologica Polonica

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1985

|

tom 36

|

nr 5-6

3

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Platelets in fibrinolytic system

100%

Korbut R., Gryglewski R. J.

Journal of Physiology and Pharmacology

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1995

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tom 46

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nr 4

4

The endothelium-dependent and the endothelium-independent vasodilators in the isolated, perfused guinea pig heart

100%

Chlopicki S., Gryglewski R. J.

Journal of Physiology and Pharmacology

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1992

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tom 43

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nr 4

The endothelium-dependent (acetylcholine, bradykinin, substance P) and the endothelium-independent (gliceryl trinirate, 3-morpholinsydnominine, sodium nitroprusside) vasodilators were studied in the Langendorff-perfused heart of the guinea pig. The involvement of prostanoids and EDRF in the endothelium-dependent responses were assessed by using indomethacin, an inhibitor of cyclooxygenase, and NG -nitro-L-Arginine, an inhibitor of NO synthase. The endothelium-independent agents were used as reference compounds. Both indomethacin and NG -nitro- L-Arginine elevated significantly baseline coronary perfusion pressure, indicating that prostanoids (most likely PGI₂ and PGE₂ ) and EDRF modulate the resting tone of the guinea pig coronary circulation. NG-nitro-L-Arginine, but not indomethacin, considerably reduced receptor-stimulated responses. It is concluded that acetylcholine, bradykinin or substance P-induced vasodilation is mediated by EDRF. In contrast, prostanoids do not contribute to endothelium-dependent responses. In addition, short-term tachyphylaxis to bolus injection of gliceryl trinitrate but not of sodium nitroprusside was demonstrated, suggesting that this preparation may be of value for studying nitrate tolerance.

5

The effect of prostacyclin and nitric oxide on deformability of red blood cells in septic shock in rats

100%

Korbut R., Gryglewski R. J.

Journal of Physiology and Pharmacology

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1996

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tom 47

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nr 4

6

Kallikrein-thrombolytic and hypotensive action in cats - preliminary results

81%

Swies J., Grodzinska L., Slawinski M., Gryglewski R. J.

Acta Physiologica Polonica

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1990

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tom 41

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nr 1-3

Święs J., Grodzińska L., Sławiński M., Gryglewski R. J.: Kallikrein-thrombolytic and hypotensive action in cats - preliminary results. Acta Physiol. Pol. 1990, 41 (1-3): 87-95. An intravenous injection of kallikrein produced hypotensive and thrombolytic effects in anasthetized cats, using the blood superfused tendon technique. The thrombolytic action of kallikrein was mediated by an unstable substance. The generation of this substance was abolished by either acetylsalicylic acid (ASA) or aprotonin and enhanced by captopril. The hypotensive action of kallikrein was only partially inhibited by ASA. It is proposed that both these pharmacological effects of kallikrein are mediated by bradykinin which in turn releases prostacyclin from the endothelium. However, in contrast to the thrombolytic effect of kallikrein which is totally mediated by prostacyclin the hypotensive action of kallikrein depends not only on prostacycylin but also on another endothelium-derived vasorelaxant, e.g. EDRF.

7

NO-dependent vasodilation induced by nebivolol in coronary circulation is not mediated by beta-adrenoceptors or by 5 HT 1A-receptors

81%

Chlopicki S., Kozlovski V. I., Gryglewski R. J.

Journal of Physiology and Pharmacology

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2002

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tom 53

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nr 4,1

Nebivolol is a unique ß1-adrenoceptor antagonist which possesses peripheral vasodilator properties dependent on endothelial NO. Nebivolol-induced release of NO was attributed to its L stereoisomer and to its ability to stimulate endothelial ß2, ß3 adrenoceptors or 5-HT1A receptors. Here, in the isolated guinea pig heart we analysed coronary vasodilator potency of L- and D-nebivolol and a possible role of ß2, ß3 adrenoceptors and 5-HT1A receptors in nebivolol-induced vasodilation. Surprisingly, we found that not only L-nebivolol (3-30x10-6 M) but also D-nebivolol (3-30x10-6 M) induced coronary vasodilation, and both responses were inhibited by L-NAME (10-4 M). In contrast with the stereoisomers of nebivolol, atenolol at the equimolar concentrations did induce slight vasoconstriction. The nonselective ß1/ß2- adrenoceptor antagonist - nadolol (10-5 M), the selective ß3-adrenoceptor antagonist - L 748337 (10-6 M) and the 5 HT1A receptor antagonist - NAN 190 (5 x 10-6 M), none of them inhibited coronary vasodilation induced by D- and L-nebivolol. In summary, in the isolated guinea pig heart both D- and L-nebivolol act as coronary vasodilators. Coronary vasodilation induced by stereoisomers of nebivolol is mediated by endothelium-derived NO and does not depend on ß2, ß3 adrenoceptors or 5 HT1A receptors.

8

Effects of nitric oxide and prostacyclin on deformability and aggregability of red blood cells of rats ex vivo and in vitro

81%

Starzyk D., Korbut R., Gryglewski R. J.

Journal of Physiology and Pharmacology

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1999

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tom 50

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nr 4

9

Reversal of the postischaemic suppression of coronary function in perfused guinea pig heart by ischaemic preconditioning

81%

Chlopicki S., Lomnicka M., Gryglewski R. J.

Journal of Physiology and Pharmacology

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1999

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tom 50

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nr 4

10

The role of nitric oxide in regulation of deformability of red blood cells in acute phase of endotoxaemia in rats

81%

Starzyk D., Korbut R., Gryglewski R. J.

Journal of Physiology and Pharmacology

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1997

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tom 48

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nr 4

11

Thrombolytic and antiplatelet action of Xanthinol nicotinate [Sadamin]: possible mechanisms

81%

Bieron K., Swies J., Kostka-Trabka E., Gryglewski R. J.

Journal of Physiology and Pharmacology

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1998

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tom 49

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nr 2

12

Interleukin 1beta induces functional prostaglandin E synthase in cultured human umbilical vein endothelial cells

81%

Uracz W., Uracz D., Olszanecki R., Gryglewski R. J.

Journal of Physiology and Pharmacology

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2002

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tom 53

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nr 4,1

Prostaglandin endoperoxide H2 (PGH2) is generated from arachidonic acid by either constitutive (COX-1) or inducible (COX-2) cyclooxygenases. In arterial wall PGH2 is converted by PGI2 synthase (PGI-S) to prostacyclin (PGI2), and in platelets by thromboxane synthase (TX-S) to thromboxane (TXA2). Other prostanoids as PGD2, PGF2alpha or PGE2 were believed to arise non-enzymatically from PGH2. Only recently, human prostaglandin E synthase (PGE-S) has been identified and cloned as a membrane bound, microsomal, glutathione-dependent inducible enzyme. Here we demonstrated that interleukin 1ß (IL-1ß) is an inducer of COX-2 and PGE-S in human umbilical vein endothelial cells (HUVEC). Functional expression of PGE-S was measured at the level of specific mRNA by semi-quantitative RT-PCR, PGE-S protein was detected by Western blot in HUVEC, while PGE2 was measured by immunoassay in the supernatant. Actinomycin D, a classical transcription inhibitor, was used to prove that indeed IL-1ß induced the functional PGE-S enzyme. PGE2 generation in HUVEC was inhibited by indomethacin, acetamoniphen and dexamethasone. In conclusion, we found that in cultured endothelial cells IL-1ß induced as evidenced by the appearance of its transcript and its functional enzyme. The induction of endothelial PGE-S and COX-2 appeared to be and their transcripts were induced as fast as one might expect from immediate early genes. It means that IL-1ß-triggered-PGE2 biosynthesis in endothelial cells is probably regulated by induction of both COX-2 and PGE-S. This is way we hypothesise the existence of at least two distinct pools of COX-2: the first selectively coupled to PGE-S and the second one that is coupled to PGI-S yielding the main endothelial product - PGI2.

13

Clonidine-induced coronary vasodilatation in isolated guinea pig heart is not mediated by endothelial alpha2 adrenoceptors

81%

Chlopicki S., Kozlovski V. I., Gryglewski R. J.

Journal of Physiology and Pharmacology

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2003

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tom 54

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nr 4

Functional role of endothelial alpha2-adrenoceptor in coronary circulation remains unclear. Clonidine, an agonist of alpha2-adrenoceptors, was reported to induce coronary vasodilatation via stimulation of endothelial alpha2-adrenoceptors or coronary vasoconstriction involving vascular smooth muscle alpha2-adrenoceptors. Moreover, H2 receptor-dependent responses to clonidine were described. Here, we reassess the contribution of endothelial alpha2-adrenoceptor and H2 receptors to coronary flow and contractility responses induced by clonidine in the isolated guinea pig heart. We found that clonidine (10-9 - 10-6 M) produced concentration-dependent coronary vasoconstriction without a significant change in contractility. This response was inhibited by the alpha1/alpha2-adrenoceptor antagonist - phentolamine (10-5 M) and the selective alpha2-adrenoceptor antagonist yohimbine (10-6 M), but it was not changed by the selective alpha1-adrenoceptor antagonist prazosin (10-6 M). In the presence of nitric oxide synthase inhibitor, L-NAME (10-4 M) the clonidine-induced vasoconstriction was potentiated. Clonidine at high concentrations of 10-5 – 3 x 10-5 M produced coronary vasodilatation, and an increase in myocardial contractility. These responses were abolished by a selective H2-receptor antagonist, ranitidine (10-5 M), but not by phentolamine (10-5 M). We conclude that in the isolated guinea pig heart, clonidine-induced vasoconstriction is mediated by activation of smooth muscle alpha2-adrenoceptors whereas clonidine-induced coronary vasodilatation is mediated by activation of vascular H2 histaminergic receptors. Accordingly, endothelial alpha2-adrenoceptors does not seem to play a major role in coronary flow response induced by clonidine.

14

Kinins and thrombolysis

81%

Swies J., Chlopicki S., Gryglewski R. J.

Journal of Physiology and Pharmacology

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1993

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tom 44

|

nr 2

15

Permissive effect of molsidomine towards cardioprotective action of iloprost in myocardial ischaemia in cats

81%

Gryglewski R. J., Swies J., Chlopicki S., Niezabitowski P.

Journal of Physiology and Pharmacology

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1993

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tom 44

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nr 3

16

Role of thromboxane A2 and platelet activating factor in early haemodynamic response to lipopolysaccharide in rats

81%

Bochenski J., Chlopicki S., Gryglewski R. J.

Journal of Physiology and Pharmacology

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1999

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tom 50

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nr 2

17

The effect of nitric oxide donors on the release of plasminogen activator inhibitor [PAI] from rabbit platelets in vitro

81%

Korbut R., Marcinkiewicz E., Cieslik K., Gryglewski R. J.

Journal of Physiology and Pharmacology

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1995

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tom 46

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nr 1

18

Increased pneumotoxicity of lipopolysaccharide from E.coli in nitric oxide deficient blood-perfused rat lungs

81%

Bartus J. B., Chlopicki S., Gryglewski R. J.

Journal of Physiology and Pharmacology

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1997

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tom 48

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nr 4

19

Paradoxical augmentation of bradykinin-induced vasodilatation by xanthine-xanthine oxidase-derived free radicals in isolated guinea pig heart

81%

Olszanecki R., Kozlovski V. I., Chlopicki S., Gryglewski R. J.

Journal of Physiology and Pharmacology

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2002

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tom 53

|

nr 4,1

Increased generation of reactive oxygen species contribute to endothelial dysfunction in atherosclerosis, hypertension and heart failure. Recently, it was suggested that bursts of superoxide anions may inactivate endothelial surface-bound enzymes such as angiotensin converting enzyme (ACE). Here, we tested effects of xanthine/xanthine oxidase-derived superoxide anions on vascular responses and ACE activity in the isolated guinea pig heart. We analysed effects of intracoronary infusion of low concentration of xanthine oxidase (10 mU/ml) in the presence of xanthine (0,5 mM) (X/XO) on bradykinin, other endothelium-dependent and independent vasodilators (acetylcholine, ADP, SNAP), as well as vasoconstrictor responses to angiotensin I and angiotensin II. Surprisingly, X/XO significantly augmented coronary response to bradykinin without an effect on responses to ADP, acetylcholine, SNAP, angiotensin I and angiotensin II. In contrast, inhibition of ACE by perindoprilate (100 nM) resulted in augmentation of bradykinin-induced vasodilatation as well as diminution of angiotensin I-evoked vasoconstriction without an influence on other responses. In summary, in the isolated guinea pig heart, X/XO-derived free radicals selectively augmented coronary vasodilator response to bradykinin, which cannot be explained by X/XO- induced derangement of ACE. The mechanism of this paradoxical phenomenon, which might represent a defensive response of the coronary circulation to oxidative stress requires further investigations.

20

Flavonoids and nitric oxide synthase

81%

Olszanecki R., Gebska A., Kozlovski V. I., Gryglewski R. J.

Journal of Physiology and Pharmacology

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2002

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tom 53

|

nr 4,1

Induction of NOS-2 in macrophages and smooth muscles within vascular wall with concomittant suppression of endothelial NOS-3 activity is considered to be a hallmark of vascular inflammation that triggers atherogenesis. Accordingly, drugs designed to reverse these changes should not only support vaning function of NOS-3 but also suppress proinflammatory NO production by NOS-2. It means that using selective inhibitors of induction of NOS-2 (they spare ex definitione constitutive activity of NOS-3) is a more rational approach than using isselectivel. inhibitors of activity of previously induced NOS-2. First of all, those drugs are never sufficiently selective. In our work we tried to identify inhibitors of NOS-2 induction within the group of flavonoids, known stimulators of NOS-3 with putative antiatherogenic effects. Representatives of four main groups of flavonoids: flavonols (kaempferol, quercetin, rutin), flavones (apigenin, primuletin), flavanols (catechine) and flavanones (hesperetin, hesperidin, naringenin) were tried on NOS-2 induction and activity in the in vitro model of LPS-treated macrophages (cell line J774.2). While none of these compounds inhibited activity of NOS-2, all with unexpectedly scattered potencies inhibited induction of NOS-2 protein in LPS-treated J774.2 cells, as evidenced by Western blotting technique. Subsequently, RT-PCR and Northern blotting methods revealed that so far the most potent compounds, kaempferol and apigenin, at micromolar concentrations did inhibit NOS-2 induction at the level of NOS-2 gene transcription. We conclude that some of flavonoids are potent inhibitors of NOS-2 induction. At the same time they may increase endothelial NOS-3 activity. Could these flavonoids become natural parents of future drugs, which will be used for reversal of inflammatory component of atherothrombosis?

Ograniczanie wyników

Anti-aggregatory prostanoids. Part II

Anti-aggregatory prostanoids. Part I

Platelets in fibrinolytic system

The endothelium-dependent and the endothelium-independent vasodilators in the isolated, perfused guinea pig heart

The effect of prostacyclin and nitric oxide on deformability of red blood cells in septic shock in rats

Kallikrein-thrombolytic and hypotensive action in cats - preliminary results

NO-dependent vasodilation induced by nebivolol in coronary circulation is not mediated by beta-adrenoceptors or by 5 HT 1A-receptors

Effects of nitric oxide and prostacyclin on deformability and aggregability of red blood cells of rats ex vivo and in vitro

Reversal of the postischaemic suppression of coronary function in perfused guinea pig heart by ischaemic preconditioning

The role of nitric oxide in regulation of deformability of red blood cells in acute phase of endotoxaemia in rats

Thrombolytic and antiplatelet action of Xanthinol nicotinate [Sadamin]: possible mechanisms

Interleukin 1beta induces functional prostaglandin E synthase in cultured human umbilical vein endothelial cells

Clonidine-induced coronary vasodilatation in isolated guinea pig heart is not mediated by endothelial alpha2 adrenoceptors

Kinins and thrombolysis

Permissive effect of molsidomine towards cardioprotective action of iloprost in myocardial ischaemia in cats

Role of thromboxane A2 and platelet activating factor in early haemodynamic response to lipopolysaccharide in rats

The effect of nitric oxide donors on the release of plasminogen activator inhibitor [PAI] from rabbit platelets in vitro

Increased pneumotoxicity of lipopolysaccharide from E.coli in nitric oxide deficient blood-perfused rat lungs

Paradoxical augmentation of bradykinin-induced vasodilatation by xanthine-xanthine oxidase-derived free radicals in isolated guinea pig heart

Flavonoids and nitric oxide synthase