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1

Cerivastatin potentiates nitric oxide release and eNOS expression through inhibition of isoprenoids synthesis

100%

Kalinowski L., Dobrucki I. T., Malinski T.

Journal of Physiology and Pharmacology

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2002

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tom 53

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nr 4,1

Endothelium dysfunction, which is often defined as a decrease in NO bioavailability, is one of the earliest manifestations of endothelium-impaired function disorders, including atherosclerosis. Although improvement in NO bioavailability has been attributed to the lowering of serum cholesterol levels, recent studies suggest that HMG-CoA reductase inhibitors, statins, may have direct effects on NO bioavailability by little known mechanisms that are independent of serum cholesterol levels. The long-term effect of cerivastatin on NO release from endothelial cells was determined by using highly sensitive electrochemical microsensors and was correlated with endothelial NO synthase (eNOS) levels. To explore whether changes in isoprenoid synthesis affect NO bioavailability and eNOS expression, human endothelial cells were treated with cerivastatin, L-mevalonate (MVA; 1.5 mmol/L), geranylgeranylpyrophosphate (GGPP; 1 mg/mL) and farnesylpyrophosphate (FPP; 1 mg/mL). Cerivastatin increased spontaneous (by 53% ±6) and an eNOS-stimulated NO release (by 41 ±6% for calcium ionophore and by 47±5% acetylcholine) as well as eNOS expression (by 118 ±6%) in the same concentration-range. Cerivastatin- dependent increase in both NO release and eNOS expression was revealed after ~4 h of exposure reaching the maximum after ~10 h. Co-treatment with MVA or GGPP, but not FPP or LDL, reversed the effects of cerivastatin. These findings indicate that the long-term effect of cerivastatin resulting in enhanced NO bioavailabilty in endothelial cell is, at least in part, due to up-regulation of eNOS by blocking isoprenoids synthesis.

2

Corneal endothelial cell cultures

88%

Rzymowska J., Gawron A., Swiech-Zubilewicz A., Pawlikowska-Pawlega B.

Folia Histochemica et Cytobiologica. Supplement

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1997

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tom 35

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nr 2

3

Control of the circulation by chemical mediators from the endothelium

88%

Vane J. R., Botting R. M.

Journal of Physiology and Pharmacology. Supplement

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1993

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tom 44

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nr 2

4

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Experimental allogenic transplantation of cornea endothelial cells in cats

75%

Kielbowicz Z., Kuryszko J., Strzadala L.

Polish Journal of Veterinary Sciences

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2010

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tom 13

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nr 4

Background: The aim of the present study was assessing the possibility of experimental allogenic transplantation of cat cornea endothelial cells, multiplied in vitro, into the anterior chamber of the eyeball in recipient cats. The reason for undertaking the research is the need to develop a method that would help in the cornea treatment in animals with corneal opacification following cataract surgery, as well as lens dislocation, injuries and endothelium degeneration. Methods: Cats aged 10-12 months were used in the experiment. Cornea fragments consisting of the posterior limiting membrane and posterior epithelium were placed in Iscove;s medium with addition of 10% foetal calf serum. Multiplied in vitro cells were injected into the anterior chamber of recipient cats. The cornea was subject to histological, histometric and SEM examination on the 3rd, 7th, 20th and 30th day after the surgery. Results: Micromorphological examination of the cornea showed full restitution of its endothelium 30 days after transplantation. Complete regeneration of structures indispensable for normal functioning of the posterior epithelium occurred as a result of implantation. Conclusions: In this study the results show that implantation of the cells of posterior corneal epithelium of donor cats, multiplied into vitro and injected into the anterior chamber of recipient cats. The cornea regained its full function, the layer of the posterior epithelium was regenerated and the stroma stabilized, presenting the image of full and proper corneal translucency.

5

Quantification of the potencies of EDRF-releases from isolated rabbit aortic strips

75%

Trybulec M., Dudek R., Radziszewski W., Swierkosz T., Zembowicz A.

Acta Physiologica Polonica

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1990

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tom 41

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nr 1-3

Trybulec M., Dudek R., Radziszewski W., Świerkosz T, Zembowicz A.: Quantification of the potencies of EDRF-releasers from isolated rabbit aortic strips. Acta Physiol. Pol. 1990, 41(1-3): 78-86. We have compared several known releasers of endothelium-derived relaxing factor (EDRF)(13) in respect to their potencies to generate EDRF by endothelium of rabbit aortic strips (RbA) superfused with Krebs’ buffer. The vasorelaxation by EDRF which is equivalent to 10 pmoles of GTN was evoked by 0.7 pmoles of substance P(SP), 50 pmoles of acetylcholine (Ach), 521 pmoles of calcium ionophore A 23187, 2720 pmoles of ADP. Threshold potencies of these agonists are inversely proportional to the maximum amount of EDRF released. Phospholipase C (PLC) from Clostridium perfringens at a dose of 0.1 U caused the relaxation of a similar magnitude. Phospholipase A2 (1 U), thrombin (1 U), bradykinin (30 nmoles) and serotonin (10 pmoles) did not release EDRF. It is concluded that endothelial cells of RbA differ from endothelial cells of other species in their susceptibility to release EDRF in response to various agonists.

6

Labile products of vascular endothelium as mediators and modulators of the functions of the central nervous system

75%

Dembinska-Kiec A., Goscinski I., Szczudlik A.

Journal of Physiology and Pharmacology

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1994

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tom 45

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nr 2

7

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

75%

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.

8

Adeno-associated virus vector-mediated gene delivery to the vasculature and kidney

75%

Kapturczak M. H., Chen S., Agarwal A.

Acta Biochimica Polonica

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2005

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tom 52

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nr 2

Relatively successful elsewhere, gene delivery aimed at the vasculature and kidney has made very little progress. In the kidney, the hurdles are related to the unique structure-function relationships of this organ and in the blood vessels to a variety of, mostly endothelial, factors making the delivery of transgenes very difficult. Among gene-therapeutic approaches, most viral gene delivery systems utilized to date have shown significant practical and safety-related limitations due to the level and duration of recombinant transgene expression as well as their induction of a significant host immune response to vector proteins. Recombinant adeno-associated virus (rAAV) vectors appear to offer a vehicle for safe, long-term transgene expression. rAAV-based vectors are characterized by a relative non-immunogenicity and the absence of viral coding sequences. Furthermore, they allow for establishment of long-term latency without deleterious effects on the host cell. This brief review addresses problems related to transgene-delivery to kidney and vasculature with particular attention given to rAAV vectors. The potential for gene therapy as a strategy for selected renal and vascular diseases is also discussed.

9

Saline containing phosphatidylcholine liposomes possess the ability to restore endothelial function damaged resulting from gamma-irradiation

75%

Soloviev A. I., Stefanov A. V., Tishkin S. M., Khromov A. S., Parshikov A. V., Ivanova I. V., Gurney A. M.

Journal of Physiology and Pharmacology

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2002

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tom 53

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nr 4,1

The protective action of passive saline filled ("empty") phosphatidylcholine liposomes (PCL) on endothelial function was examined in thoracic aortas obtained from gamma irradiated (6 Gy) Chinchilla rabbits, and then verified in experiments on non-anesthetized and anesthetized rats. Acetylcholine (ACh)-induced vascular relaxant responses in isolated vascular tissues rats were used as the test of endothelial integrity and its functional ability. It was shown that when added to the bath solution (100 µg/ml), PCL effectively restored endothelium-dependent ACh relaxations of isolated vascular rings damaged resulting from -irradiation but had no effect on endothelium-independent vascular responses to therapeutic nitric oxide (NO) donors. The liposomes were also without protective effect when injected to the rabbits intraperitoneally (30 mg/kg) 1 hour before irradiation. In contrast, PCL, being injected at the same dose 1 hour after radiation impact, promote normalization of both endothelium-dependent vascular responses to ACh and nitric oxide (NO) donors. PCL restored also the sensitivity of vascular tissues to authentic NO (aqueous NO solution) that was surprisingly increased after irradiation, and normalized relationship between ACh-stimulated NO release and relaxant response amplitudes in irradiated aortas. Experiments on non-anesthetized and anesthetized rats demonstrated that irradiation led to significant elevation in the level of arterial blood pressure without any changes in cardiac contractility. PCL administration (25 mg/kg, i.v.) effectively normalized an increased arterial blood pressure in irradiated animals. In conclusion, it appears that PCL due to its ability to normalize NO- dependent vascular tone control mechanisms might be worthwhile therapeutic approach in case of ionizing irradiation accident. These result support the concept that the depression of endothelium-dependent vascular responses after irradiation may be result of decreased NO bioavailability due to its conversion to less potent vasodilators during irradiation-induced oxidative attack.

10

Actions and interactions of endothelins, prostacyclin and nitric oxide in the gastric mucosa

75%

Whittle B. J. R., Lopez-Belmonte J.

Journal of Physiology and Pharmacology

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1993

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tom 44

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nr 2

11

Superoxide dismutase activity and expression in human venous and arterial bypass graft vessels

75%

Guzik T. J., Olszanecki R., Sadowski J., Kapelak B., Rudzinski P., Jopek A., Kawczynska A., Ryszawa N., Loster J., Jawien J., Czesnikiewicz-Guzik M., Channon K. M., Korbut R.

Journal of Physiology and Pharmacology

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2005

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tom 56

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nr 2

Venous bypass grafts are more prone to accelerated atherosclerosis than arterial grafts, which is partly related to increased oxidative stress and diminished nitric oxide bioavailability. In veins superoxide production is dependent primarily on nox2 NAD(P)H oxidase expression, while in arteries nox4 appears to play an important role. This may in part explain differences in susceptibility to graft failure. Net levels of oxidative stress are however determined in parallel by the production as well as by degradation of free radicals (eg. by superoxide dimutases, catalases, thioredoxins etc). The differences in superoxide dismutase (SOD) expression and activity in human bypass conduit vessels remain unclear. Accordingly, we aimed to compare SOD activity and protein levels as well as its functional effects on superoxide production in segments of human internal mammary arteries (IMA) and saphenous veins (HSV) from patients undergoing bypass graft surgery (n=24). SOD activity was assessed by inhibition of pyrogallol autoxidation, Cu-Zn SOD and Mn SOD protein levels were studied by immunoblotting. Basal superoxide release was detected by lucigenin (5µM) enhanced chemiluminescence. Total SOD activity did not differ significantly between HSV and IMA. Similarly, no difference was observed in SOD activity in the presence of KCN (Mn-SOD). Human bypass conduit vessels show amounts of Cu-Zn SOD or Mn-SOD protein levels. In both HSV and IMA segments superoxide production was more than doubled in the presence of SOD inhibitor - DETC. Conclusions: These studies suggest that the differences in oxidative stress between human arteries and veins are unlikely to be caused by SOD activity. However SOD plays and important role in amelioration of oxidative stress in both types of vessels.

12

Production of prostacyclin and prostaglandin E2 in resting and IL-1beta-stimulated A549, HUVEC and hybrid EA.HY 926 cells

75%

Olszanecki R., Gebska A., Korbut R.

Journal of Physiology and Pharmacology

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2006

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tom 57

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nr 4

Production of arachidonic acid (AA) metabolites - prostacyclin (PGI2) in large vessels and prostaglandin E2 (PGE2) in microcirculation is intrinsically involved in maintenance of vascular wall homeostasis. EA.hy 926 is a hybrid cell line, is derived by fusion of HUVEC with A549 cells. The aim of this study was to examine the production of prostacyclin and PGE2 in resting and IL-1ß-stimulated EA.ha 926 cells, in comparison with its progenitor cells. Non-stimulated EA.hy 926 cells has been found to produce much lower amounts of prostacyclin than resting HUVEC. Resting hybrid cells produced more PGE2 than prostacyclin, despite they expressed high levels of COX-1 and PGI2 synthase. On the contrary to HUVEC and A549, EA.hy 926 cells did not respond to IL-1ß with COX-2 induction and increase of prostaglandin production, however they did it in response to lysophosphatidylcholine (LPC). The characteristics of EA.hy 926 cells in terms of the pattern of prostanoid formation could facilitate studies on endothelial metabolism and role of these important lipid mediators.

13

Secretory functions of the vascular endothelium

75%

Vane J. R., Botting R. M.

Journal of Physiology and Pharmacology

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1992

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tom 43

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nr 3

The endothelial cells which line the blood vessels as a monolayer exert a remarkable control over the vascular system. Indeed, the endothelium can be regarded as a highly active metabolic and endocrine organ in its own right. On the hand, vasoactive substances such as serotonin and bradykinin are inactivated and on the other the cells can enzymatically produce the vasoconstrictor, angiotensin II and secrete endothelin-1 ((ET-1). Perhaps more importantly, the cells also produce two unstable vasodilator substances, which potently inhibit platelet clumping: prostacyclin and endothelium-derived relaxing factor (EDRF) which has been identified as nitric oxide (NO; 1). Both substances seem well designated as local hormones, released to influence adjacent cells. The endothelial cell, therefore, exerts control over the cardiovascular system by elaborating dilator substances as well as vasconstrictors.

14

Developmental changes in endothelium-dependent relaxation of the chicken ductus arteriosus

75%

Agren P., Van Der Sterren S., Cogolludo A. L., Frazziano G., De Mey J. G. R., Blanco C. E., Villamor E.

Journal of Physiology and Pharmacology

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2008

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tom 59

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nr 1

We tested the hypothesis that endothelium-dependent relaxation in the chicken ductus arteriosus (DA) is developmentally regulated. Isolated DA rings from 15-, 19- and 21-day-old (externally pipped) chicken embryos relaxed to acetylcholine (ACh). This relaxation was unaffected by indomethacin but impaired by endothelium removal, by the NO synthase inhibitor L-NAME, and by the soluble guanylate cyclase inhibitor ODQ, suggesting the involvement of NO. This NO production was confirmed with the fluorescent probe DAF-2DA. The combination of apamin and charybdotoxin with L-NAME produced a further inhibition of ACh-induced relaxation, suggesting the participation of a putative EDHF. In the 21-day DA, the relaxations induced by ACh and sodium nitroprusside (SNP) were markedly reduced and scanning electron microscopy demonstrated an irregular endothelial lining with protrusion and detachment of endothelial cells. The relaxations induced by BAY 41-2272 and 8-Br cGMP were not affected by age. When compared with 5%, lower (0%) and higher (21, 95%) O2 concentrations impaired ACh-induced relaxation. In summary, we found that ACh induces endothelium-dependent relaxation of the chicken DA and that NO and EDHF are involved in this response. During chicken DA closure, endothelial cells undergo morphologic and functional alterations that result in the lack of endothelium-dependent relaxation.

15

Carboxyebselen a potent and selective inhibitor of endothelial nitric oxide synthase

75%

Hatchett R. J., Gryglewski R. J., Mlochowski J., Zembowicz A., Radziszewski W.

Journal of Physiology and Pharmacology

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1994

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tom 45

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nr 1

16

Ultrastructural alterations of endothelium covering advanced atherosclerotic plaque in human carotid artery visualised by scanning electron microscope

75%

Walski M., Chlopicki S., Celary-Walska R., Frontczak-Baniewicz M.

Journal of Physiology and Pharmacology

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2002

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tom 53

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nr 4,1

Human atherosclerotic plaque morphology at its various stages was extensively documented using light microscopy. However, much less is known of the ultrastructure of the human atherosclerotic plaque, in particular of ultrastructure of endothelial cells in atherosclerosis. Here, we analysed alterations of endothelial cells covering advanced atherosclerotic plaque in carotid artery using scanning electron microscope. Examination was performed on specimens from atherosclerotic lesions of the interior carotid artery, collected from 8 patients who had undergone endarterectomy. We found wide spectrum of pathological alterations of the luminal surface of atherosclerotic plaque. In dominant part of the vessel, endothelial layer was preserved but displayed pronounced irregularities in endothelial architecture including appearance of cuboidal cells. Some endothelial cells were covered by numerous microvilli and/or contained "craters" disrupting continuous surface of the endothelium. Platelets and leukocytes adhering to endothelium were frequently observed. There were also areas of the vessel lumen with endothelial denudation, in which the subendothelial surface containing fibrin proteins and collagen fibrils were visible. Interestingly, signs of proliferation of endothelial cells tending to cover the partially denuded vessel were observed. In summary, in scanning electron microscope, preserved endothelial cells of advanced atherosclerotic plaque displayed pronounced pathology; whether any of these changes represent the ultrastructural correlate of endothelial dysfunction remains to be established.

17

Role of adhesion molecules in chronic allograft rejection

75%

Nowaczyk M., Gorski A., Durlik M., Wyzgal J., Perkowska-Francka A.

Archivum Immunologiae et Therapiae Experimentalis

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1999

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tom 47

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nr 6

18

Soluble selectin profiles associated with severe trauma

75%

Siemiatkowski A., Rogowski F., Wereszczynska-Siemiatkowska U., Malinowska L., Borkowski J.

Archivum Immunologiae et Therapiae Experimentalis

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2001

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tom 49

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nr 4

19

Nitric oxide signalling in the cardiovascular system - physiology and pathology

75%

Malinski T.

Postępy Higieny i Medycyny Doświadczalnej

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1999

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tom 53

|

nr 2

20

Regular exercise alleviates renovascular hypertension-induced cardiac/endothelial dysfunction and oxidative injury in rats

63%

Kumral Z. N. O., Sener G., Ozgur S., Koc M., Suleymanoglu S., Hurdag C., Yegen B. C.

Journal of Physiology and Pharmacology

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2016

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tom 67

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nr 1

Ograniczanie wyników

Cerivastatin potentiates nitric oxide release and eNOS expression through inhibition of isoprenoids synthesis

Corneal endothelial cell cultures

Control of the circulation by chemical mediators from the endothelium

Experimental allogenic transplantation of cornea endothelial cells in cats

Quantification of the potencies of EDRF-releases from isolated rabbit aortic strips

Labile products of vascular endothelium as mediators and modulators of the functions of the central nervous system

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

Adeno-associated virus vector-mediated gene delivery to the vasculature and kidney