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Bakar, N., Algan, G. (1997) Electron microscopic examination of the development of the endothelium in Trifolium pratense L. during embryogenesis. Turkish J. Botany 21 , 137–144. Algan G

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) 9. Furchgott RF , Vanhoutte PM : Endothelium-derived relaxing and contracting factors . FASEB J. 3 , 2007 – 2018 ( 1989 ) 10

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little was known about the role played by the endothelium in vascular reactivity during moderate hypothermia. Human varicose spermatic vein is an easily accessible smooth muscle preparation but the studies on this vessel are limited and the effects of

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In recent years, pyridine nucleotides NAD(H) and NADP(H) have been established as an important molecules in physiological and pathophysiological signaling and cell injury pathways. Protein modification is catalyzed by ADP-ribosyl transferases that attach the ADP-ribose moiety of NAD+ to specific aminoacid residues of the acceptor proteins, with significant changes in the function of these acceptors. Mono(ADP-ribosyl)ation reactions have been implicated to play a role both in physiological responses and in cellular responses to bacterial toxins. Cyclic ADP-ribose formation also utilizes NAD+ and primarily serves as physiological, signal transduction mechanisms regulating intracellular calcium homeostasis. In pathophysiological conditions associated with oxidative stress (such as various forms of inflammation and reperfusion injury), activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) occurs, with subsequent, substantial fall in cellular NAD+ and ATP levels, which can determine the viability and function of the affected cells. In addition, NADPH oxidases can significantly affect the balance and fate of NAD+ and NADP in oxidatively stressed cells and can facilitate the generation of various positive feedback cycles of injury. Under severe oxidant conditions, direct oxidative damage to NAD+ has also been reported. The current review focuses on PARP and on NADPH oxidases, as pathophysiologically relevant factors in creating disturbances in the cellular pyridine nucleotide balance. A separate section describes how these mechanisms apply to the pathogenesis of endothelial cell injury in selected cardiovascular pathophysiological conditions.

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Acta Physiologica Hungarica
Authors:
Z Oreščanin
,
Z Oreščanin
,
Z Oreščanin
,
SR Milovanović
,
SR Milovanović
, and
SR Milovanović

In the present study we investigated the mechanism of nitric oxide induced relaxation of renal arteries, with or without endothelium, taken from normotensive and spontaneously hypertensive (SH) rats. With this purpose in mind, the effects of the nitric oxide donor, sodium nitroprusside (SNP), with and without L-arg in the medium, on isolated rat renal artery relaxation were studied. Relaxing effect of SNP was higher in normotensive (10-5 M of SNP caused 220% of relaxation in the cases with endothelium and 240% without endothelium), in comparison with SH rats (100% of relaxation with endothelium and 150% without). L-arg antagonized the relaxing effect of SNP in the examined renal arteries, more in normotensive (100-160% with endothelium and 110-195% without) than in hypertensive ones (0-10% with endothelium and 35-75% without) at SNP concentrations 10-7-10-5 M, respectively (*P<0.05; **P<0.001). L-arg did not significantly change relaxing effect of SNP in the isolated renal arteries with endothelium taken from SH rats, which show that L-arg, by modifying the chemical versatility of NO into redox active forms -nitrosonium (NO+) and -nitroxyl (NO-), produces different relaxing effects in normotensive and hypertensive isolated arteries of rats, with or without endothelium, potentiating the role of nitroxyl induced relaxation in SH rats.

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The purpose of our study was to investigate whether endothelium-derived relaxations induced by store depletion are altered in aging rat thoracic aorta. Vascular responses were measured in aortic segments isolated from young (2–4 month) and old (20–24 month) male Sprague-Dawley rats. In phenylephrine-contracted intact tissues, receptor-mediated and receptor-independent endothelium-derived relaxations were induced by acetylcholine (ACh) and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) blocker cyclopiazonic acid (CPA), respectively. In addition, CPA-induced changes in intracellular calcium levels were monitored in fura-2-loaded endothelium-denuded tissues. Real-time quantitative reverse transcription polymerase chain reaction and western blot analysis were performed to determine the transient receptor potential canonical (TRPC) 4 mRNA and protein levels. Endothelial TRPC4 mRNA levels were apparently decreased in aging rats. Immunoblot analysis showed that TRPC4 protein levels significantly decreased in intact aorta from 20- to 24-month-old rats compared to that from 2- to 4-month-old rats. ACh- and CPA-induced endothelium-dependent relaxations decreased in old rat aorta without any change in direct vasodilation induced by sodium nitroprusside. Store-operated Ca2+ entry (SOCE) induced by CPA was significantly decreased, whereas sarcoplasmic reticulum Ca2+ release was unaffected in endothelium-denuded aging rat aorta. In conclusion, TRPC4 downregulation could be associated with decreased endothelium-dependent vasorelaxations. As endothelial nitric oxide synthase is activated by SOCE-induced caveolar internalization, tracking the expression levels of SERCA, ion channels, and/or associated proteins involved in SOCE would lead to the development of novel therapeutics for age-related vasospastic disorders with dysfunctional endothelium.

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The present study was undertaken in order to examine transduction mechanism involved in the single application of 100 μM homocysteine (Hcy) on isolated rat femoral artery (RFA) rings equilibrated on the basal tone; to establish if a single application of 100 μM Hcy alters contractile effect of phenylephrine (Phe), or oppositely the relaxant effect of acetylcholine (ACh) or bradykinin (BK) after 60-min-long incubation of 100 μM Hcy; and finally to identify morphological changes on the vascular wall after a 24-h-long incubation of 100 μM Hcy. Hcy produced contractile response of intact RFA, which was increased after endothelial denudation, while decreased by urapidil (an α1 receptor blocker), nifedipine (a voltage-gated L-type Ca++ channel blocker) or indomethacin (a cyclooxygenase inhibitor). The initial RFA contraction evoked by Phe was further increased by the single addition of Hcy, which was not the case when ouabain (an inhibitor of Na+/K+-ATPase) was preincubated. After 60-min-long incubation of Hcy relaxant actions of ACh and BK were unaltered, equieffective and equipotent. A 24-h-long incubation of RFA rings with Hcy produced an impairment of vascular endothelium, expressed as a minor or more pronounced interruption of endothelial cells.

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. Torner 1988 Effects of aging and hypertension on endothelium-dependent vascular relaxation in rat carotid artery Stroke 19 892 897

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Acta Veterinaria Hungarica
Authors:
Csaba Jakab
,
Judit Halász
,
András Kiss
,
Zsuzsa Schaff
,
Attila Szász
,
Miklós Rusvai
,
Zsolt Abonyi Tóth
, and
Janina Kulka

In our recent investigation, angiogenesis was evaluated and quantified by immunohistochemical evaluation of microvessel density (MVD) using claudin-5 (CLDN-5) as a marker for vascular endothelium in 67 canine mammary gland tumours. Computer image analysis was used to measure the intratumoural MVD. Higher intratumoural MVD was detected in malignant simple neoplasms compared with benign tumours. Furthermore, the results of MVD were correlated with histological grade, higher grades being accompanied by higher MVD. In simple adenomas and grade I tubular-tubulopapillary simple carcinomas the intratumoural microvessels were wide and regular in shape with evident erythrocytes in their lumen. In grade III solid carcinomas the microvessels were smaller, less regular and had irregular shape, often without a distinct lumen, and isolated endothelial cells were frequently present. In the complex carcinomas MVD was low and the intratumoural microvessels were mostly irregular in shape without a distinct lumen. The evaluation of MVD by CLDN-5 immunohistochemistry may give useful additional information on the angiogenic potential of breast cancers in dogs.

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The afferent arteriole (AA) is an important regulatory site of renal function and blood pressure. We have demonstrated endothelial fenestration and high permeability in the vicinity of renin granulated epithelioid cells in the juxtaglomerular portion of the afferent arteriole in different mammals. The permeability of fenestrated endothelium of afferent arteriole may be important in connection to various physiologic and pathophysiologic processes. We have assumed that the permeable fenestration may serve as a communication channel between the intravascular circulation and a pathway for renin secretion. Utilising the multiphoton image technique we were able to visualise the endothelial fenestration and renin granules of the in vitro microperfused AA and in vivo AA. We demonstrated that ferritin-positive, i.e., permeable portion of the afferent arteriole, under control conditions is on average 45 μm, which is about one-third to half of the total length of the afferent arteriole. The length of this portion is not constant and can change by physiologic and pharmacologic manipulation of renin formation. The permeability of the afferent arteriole is not changing only parallel with the pharmacologically stimulated renin secretion as already demonstrated in adult rats, but also with the change of renin appearance in afferent arteriole within the very first few days of life after birth. Independently from the age there is a significant correlation between the renin-positive and permeable portion of the AA. Further studies are necessary to clarify the physiological significance of afferent arteriolar permeability and its changes in the postnatal development of the kidney, as well as in correlation with activity of renin- angiotensin system.

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