Rat Blood Vessels Research Articles

Montmorillonite adsorbs creatinine and accelerates creatinine excretion from the intestine

This study aims to evaluate the sorption by montmorillonite of creatinine and the accelerating effect of montmorillonite on creatinine excretion from the intestine. The sorption of montmorillonite was observed in vitro. Also, rat intestinal tract and blood vessels were perfused circularly with perfusate with or without creatinine, respectively, to study the promotion of creatinine diffusion from the blood vessel to the intestine and the inhibition of creatinine absorption in the intestinal tract. The effect of decreasing the serum concentration of creatinine was studied in an acute hypercreatininaemia mouse model. The concentration of creatinine was determined by the basic picric acid method. Montmorillonite adsorbed creatinine markedly in the simulated intestinal solution in a concentration-dependent manner. The sorption-time curve of montmorillonite with creatinine showed that the sorption was fast. The adsorption rate reached a maximum in 10 min. The pH of the solution influenced the sorption, the rate of which was higher at a low pH than at a high pH. Creatinine could diffuse from the blood vessel to the intestine and was reabsorbed in the intestine. Montmorillonite promoted the diffusion and inhibited the absorption. Montmorillonite decreased the serum creatinine level of hypercreatininaemia mice prepared by injecting creatinine intraperitoneally. Montmorillonite adsorbs creatinine and accelerates its excretion from the intestine.

Measuring Young’s modulus of biological objects in a liquid medium using an atomic force microscope with a special probe

A special probe with a 5-μm-diameter ball fixed at the end is developed for an atomic force microscope (AFM), with the use of which it is possible to obtain more correct values of the Young’s moduli of biological objects in liquid media and eliminate the risk of damaging the sample surface. In particular, the AFM measurements with this probe in situ revealed an increase in the Young’s modulus of rat blood vessel under the action of chlorhexidine.

Ubiquitous yet Distinct Expression of Podocalyxin on Vascular Surfaces in Normal and Tumor Tissues in the Rat

Background/Aims: The vasculature has become an important target in the development of therapies for increasing numbers of human diseases, yet there are few reliable markers available to identify the endothelium in rodent models. We have characterized the expression, subcellular localization and accessibility of the rat pan-endothelial marker podocalyxin (podxl) using a newly developed monoclonal antibody (mAb), G278. Methods: podxl expression and accessibility to binding by G278 were determined in the rat by a variety of experimental approaches. Results: mAb G278 reliably immunostained blood vessels of all types and of every size in fresh-frozen, fixed-frozen and paraffin-embedded sections of all tissues, but did not stain lymphatic vessels. Western blotting, in vivo imaging and biodistribution analyses demonstrated that the highest levels of endothelial podxl were found in the lung and heart. We also determined that podxl is not enriched in caveolae and that its expression can be modulated in the tumor microenvironment. Conclusion: Our study shows that podxl is a better identifier of rat endothelia than are some of the more commonly used markers and that mAb G278 is a robust antibody for use not only in identifying rat blood vessels but also as a tool to elucidate podxl function.

Vasodilator Effects of Ibudilast on Retinal Blood Vessels in Anesthetized Rats

Ibudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-alpha]pyridine) is clinically used as a cerebral vasodilator in Japan. However, the effects of ibudilast on retinal blood vessels have not been fully examined. The aim of this study, therefore, was to examine the effects of ibudilast on retinal blood vessels in rats in vivo. Male Wistar rats (8 to 10 weeks old) were anesthetized with thiobutabarbital (120 mg/kg, intraperitoneally (i.p.)). Retinal vascular images were captured with a fundus camera system for small animals, and the diameter of retinal blood vessels was measured. Ibudilast (0.1 and 1 mg/kg, intravenously (i.v.)) elicited a sustained increase in the diameter of retinal blood vessels and heart rate without altering systemic blood pressure. The effects of ibudilast were significantly reduced by treatment with the nonselective cyclooxygenase inhibitor indomethacin (5 mg/kg, i.p.). These results suggest that ibudilast dilates retinal blood vessels through cyclooxygenase-dependent mechanisms in rats in vivo.

Intravenously administered phosphodiesterase 4 inhibitors dilate retinal blood vessels in rats

In the present study, we examined effects of intravenously administered inhibitors of phosphodiesterase 4 (rolipram and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro-20-1724)) and non-selective inhibitor of phosphodiesterases (theophylline) on diameter of retinal blood vessel and fundus (retinal/choroidal) blood flow in rats. Male Wistar rats (8- to 10-week-old) were treated with tetrodotoxin (50 μg/kg, i.v.) to eliminate any nerve activity and prevent the eye movement under artificial ventilation. Methoxamine was used to maintain adequate systemic circulation. Ocular fundus images were captured with an original high-resolution digital fundus camera for small animals. Diameters of retinal blood vessels contained in the digital images were measured using image-processing softwares on a personal computer. Fundus blood flow was measured using a laser Doppler flow meter. Both rolipram (0.01–10 μg/kg/min, i.v.) and Ro-20-1724 (0.01–10 μg/kg/min, i.v.) increased diameters of retinal blood vessels in a dose-dependent manner without significant effect on systemic blood pressure, heart rate and fundus blood flow. The effects of phosphodiesterase 4 inhibitors on retinal arterioles were greater than those on retinal venules. Similarly, theophylline (0.1–10 mg/kg/min, i.v.) dilated retinal blood vessels, whereas it decreased blood pressure and increased heart rate markedly. These results suggest that phosphodiesterase 4 contributes to maintenance of retinal vascular tone. Inhibitors of phosphodiesterase 4 could be considered as a candidate for therapeutic drugs to treat diseases associated with disorders of retinal circulation without severe cardiovascular side-effects.

The EDHF Story

See related article, pages 1247–1255 The dilator function of the vascular endothelium is critical for optimal tissue perfusion, and this is brought into stark reality in a number of diseases, such as hypertension, diabetes, and preeclampsia, in which endothelium-dependent vasodilator function is impaired. Prostacyclin and nitric oxide (NO) were the earliest identified endothelium-dependent vasodilators, but it was soon found that in many vascular beds, particularly in resistance vessels, vasorelaxation persisted when production of these autacoids was suppressed. This residual vasorelaxation was invariably associated with hyperpolarization of the vascular smooth muscle and the entity was dubbed “endothelium-derived hyperpolarizing factor” (EDHF).1 From the outset, the identity of EDHF has been the subject of vigorous debate. Nonetheless, that the “EDHF effect” is blocked by agents that target calcium-activated K+ channels is among the few aspects of EDHF on which there is apparent consensus. There was also the debate on the significance, or otherwise, of EDHF. Is it just the poor cousin of NO, stepping into the breech when the latter is compromised, especially under conditions of enhanced oxidative stress? Then a beacon of light shone out from Japan, with the demonstration that EDHF assumed greater importance as vessel diameter decreased.2 This was a key observation, supporting the importance of EDHF in the region of the vascular system where resistance is primarily determined. This was hotly followed by the revelation that EDHF may be targeted in diseases, diabetes,3–5 hypertension,6 and apolipoprotein E-deficient mice.7 Thus, EDHF, suggested to provide vasodilation when NO was compromised, was also under attack in disease. Despite its Cinderella status, investigation into the nature of EDHF has continued with breakneck intensity, with the conviction that …

Effect of duration of force application on blood vessels in young and adult rats

Age effects on orthodontically induced periodontal vascular reactions have not been studied. The aim of the present study was to test the hypothesis that prolonged tooth movement induces age-related increases in periodontal vascularity. A standardized orthodontic appliance was placed in 2 groups of 30 rats aged 6 weeks and 9 to 12 months. At 1, 2, 4, 8, and 12 weeks, animals were killed. Blood vessels (BV) were identified based on their morphology and by immunohistochemical staining for alpha-smooth muscle actin. At each study region, surface areas (SA) of the periodontal ligament space and each BV were measured; BV mean SA, BV relative SA (the summed BV SA as a percentage of the periodontal ligament SA), and BV numbers were calculated. Pressure and tension regions showed similar vascular changes. Young rats had lower BV relative SA and BV mean SA in the early phase of force application (< 4 weeks); this increased in the late phase, reaching the same level as adult rats. In the late phase (4-12 weeks), young rats had increases of both small- and large-sized BV that did not affect the BV mean SA; adult rats had an increase of small-sized BV only; this resulted in decreased BV mean SA. The hypothesis was confirmed that prolonged tooth movement increases periodontal vascularity, which is age related. These results suggest that clinicians should consider age-related difference in tissue reactions during orthodontic tooth movement.

Estradiol Stimulates Transcription of Nuclear Respiratory Factor-1 and Increases Mitochondrial Biogenesis

Estrogen has direct and indirect effects on mitochondrial activity, but the mechanisms mediating these effects remain unclear. Others reported that long-term estradiol (E(2)) treatment increased nuclear respiratory factor-1 (NRF-1) protein in cerebral blood vessels of ovariectomized rats. NRF-1 is a transcription factor that regulates the expression of nuclear-encoded mitochondrial genes, e.g. mitochondrial transcription factor A (TFAM), that control transcription of the mitochondrial genome. Here we tested the hypothesis that E(2) increases NRF-1 transcription resulting in a coordinate increase in the expression of nuclear- and mitochondrial- encoded genes and mitochondrial respiratory activity. We show that E(2) increased NRF-1 mRNA and protein in MCF-7 breast and H1793 lung adenocarcinoma cells in a time-dependent manner. E(2)-induced NRF-1 expression was inhibited by the estrogen receptor (ER) antagonist ICI 182,780 and actinomycin D but not by phosphoinositide-3 kinase and MAPK inhibitors, indicating a genomic mechanism of E(2) regulation of NRF-1 transcription. An estrogen response element (ERE) in the NRF-1 promoter bound ER alpha and ER beta in vitro, and E(2) induced ER alpha and ER beta recruitment to this ERE in chromatin immunoprecipitation assays in MCF-7 cells. The NRF-1 ERE activated reporter gene expression in transfected cells. Small interfering RNA to ER alpha and ER beta revealed that ER alpha mediates E(2)-induced NRF-1 transcription. The E(2)-induced increase in NRF-1 was followed by increased TFAM and the transcription of Tfam-regulated mitochondrial DNA-encoded COI and NDI genes and increased mitochondrial biogenesis. Knockdown of NRF-1 blocked E(2) stimulation of mitochondrial biogenesis and activity, indicating a mechanism by which estrogens regulate mitochondrial function by increasing NRF-1 expression.

Rebuttal from Drs. Mcloughlin and Mcmurtry

POINT-COUNTERPOINTRebuttal from Drs. Mcloughlin and McmurtryPublished Online:01 Oct 2007https://doi.org/10.1152/japplphysiol.00274.2007cMoreSectionsPDF (44 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat We read with great interest the arguments put forward by Drs. Rabinovitch, Chesler, and Molthen to support their case (8). They raise a number of important issues that warrant further investigation. However, not surprisingly, we cannot agree with all that they propose. We discuss here those issues not dealt with in our original submission.Regarding the limitations of the barium-gelatin infusion technique, our opponents argue that studies in which small pulmonary arteries were identified using anti-PECAM immunostaining also report vascular loss. However, others who have used anti-von Willebrand Factor or elastin staining to identify vessels did not detect reduced vascular density in hypoxic hypertensive lungs (2, 4, 5).Dr. Rabinovitch and her coauthors next discuss studies of the pulmonary vasculature undertaken using contrast (PFOB)-based microCT imaging. While this elegant approach holds much promise for the future, we do not believe it can at present address the issue of angiogenesis or rarefaction in the lung. First, the resolution of the technique means that the smallest vessel that can be visualized is at best 70 μm in diameter (6). Second, the principal pathway analysis that this technique uses does not examine parallel distal pathways. Finally, as we have all agreed, full relaxation of vascular tone is essential for angiographic techniques to accurately detect structural changes. It seems unlikely that brief exposure to papaverine, which was used to prepare the lungs for the PFOB-microCT studies (6), could have achieved this. Rho kinase inhibitors appear to be uniquely potent in reducing vascular tone in the chronically hypoxic pulmonary circulation (3, 7), and to our knowledge transient exposure to papaverine has not been shown to be similarly effective. Thus the PFOB-microCT technique cannot provide unambiguous information regarding distal vessel number.We agree with Dr. Rabinovitch and her colleagues that Rho kinase inhibitors have only been shown to abolish chronic hypoxic pulmonary hypertension at low flow rates and their effects should be examined over a larger range of flows. They suggest that angiogenesis and precapillary arteriolar loss may occur simultaneously. Such a mechanism could reconcile seemingly disparate views on this issue and warrants further investigation. Finally, we agree that there can be major discrepancies between hemodynamic changes and structural changes in the vascular bed following chronic hypoxia. Factors such as reduced vascular compliance may contribute importantly to right ventricular overloading, although it should be recognized that, in addition to changes in structure, smooth muscle contraction can also alter compliance (1).REFERENCES1 Bank AJ, Kaiser DR. Smooth muscle relaxation: effects on arterial compliance, distensibility, elastic modulus, and pulse wave velocity. Hypertension 32: 356–359, 1998.Crossref | PubMed | ISI | Google Scholar2 Brusselmans K, Compernolle V, Tjwa M, Wiesener MS, Maxwell PH, Collen D, Carmeliet P. Heterozygous deficiency of hypoxia-induciblefactor-2alpha protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia. J Clin Invest 111: 1519–1527, 2003.Crossref | PubMed | ISI | Google Scholar3 Hyvelin JM, Howell K, Nichol A, Costello CM, Preston RJ, McLoughlin P. Inhibition of Rho-kinase attenuates hypoxia-induced angiogenesis in the pulmonary circulation. Circ Res 97: 185–191, 2005.Crossref | PubMed | ISI | Google Scholar4 Kay JM, Suyama KL, Keane PM. Failure to show decrease in small pulmonary blood vessels in rats with experimental pulmonary hypertension. Thorax 37: 927–930, 1982.Crossref | PubMed | ISI | Google Scholar5 Pascaud MA, Griscelli F, Raoul W, Marcos E, Opolon P, Raffestin B, Perricaudet M, Adnot S, Eddahibi S. Lung overexpression of angiostatin aggravates pulmonary hypertension in chronically hypoxic mice. Am J Respir Cell Mol Biol 29: 449–457, 2003.Crossref | PubMed | ISI | Google Scholar6 Molthen RC, Karau KL, Dawson CA. Quantitative models of the rat pulmonary arterial tree morphometry applied to hypoxia-induced arterial remodeling. J Appl Physiol 97: 2372–2384, 2004.Link | ISI | Google Scholar7 Nagaoka T, Morio Y, Casanova N, Bauer N, Gebb S, McMurtry I, Oka M. Rho/Rho kinase signaling mediates increased basal pulmonary vascular tone in chronically hypoxic rats. Am J Physiol Lung Cell Mol Physiol 287: L665–L672, 2004.Link | ISI | Google Scholar8 Rabinovitch M, Chesler N, Molthen C. Point: Chronic hypoxia-induced pulmonary hypertension does lead to loss of pulmonary vasculature. J Appl Physiol; doi:10.1152/japplphysiol.00274.2007.Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation More from this issue > Volume 103Issue 4October 2007Pages 1453-1454 Copyright & PermissionsCopyright © 2007 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00274.2007cHistory Published online 1 October 2007 Published in print 1 October 2007 Metrics

Rebuttal from Drs. Rabinovitch, Chesler, and Moulthen

Rebuttal from Drs. Rabinovitch, Chesler, and Moulthen

Counterpoint: Chronic Hypoxia-induced Pulmonary Hypertension does not Lead to Loss of Pulmonary Vasculature

Exposure of native sea level dwellers to chronic hypoxia due to migration to high altitude leads to the development of increased pulmonary vascular resistance causing pulmonary hypertension. In some susceptible individuals this progressively worsens causing right ventricular failure and ultimately

Angiotensinergic innervation of rat and human mesenteric resistant blood vessels

AbstractIn contrast to the current believe that angiotensin II (Ang II) only interacts with the sympathetic nervous system (SNS) as a circulating hormone, we document here the existence of an endogenous renin-angiotensin system (RAS) in the sympathetic coeliac ganglion and the angiotensinergic innervation with mesenteric resistant blood vessels. Our findings indicate that Ang II is synthesized inside the neurons of sympathetic coeliac ganglion and may act as an endogenous neurotransmitter locally on the mesenteric resistant blood vessels.

Yin Yang-1 Inhibits Vascular Smooth Muscle Cell Growth and Intimal Thickening by Repressing p21 WAF1/Cip1 Transcription and p21 WAF1/Cip1 -Cdk4-Cyclin D1 Assembly

Vascular injury initiates a cascade of phenotype-altering molecular events. Transcription factor function in this process, particularly that of negative regulators, is poorly understood. We demonstrate here that the forced expression of the injury-inducible GLI-Krüppel zinc finger protein Yin Yang-1 (YY1) inhibits neointima formation in human, rabbit and rat blood vessels. YY1 inhibits p21(WAF1/Cip1) transcription, prevents assembly of a p21(WAF1/Cip1)-cdk4-cyclin D1 complex, and blocks downstream pRb(Ser249/Thr252) phosphorylation and expression of PCNA and TK-1. Conversely, suppression of endogenous YY1 elevates levels of p21(WAF1/Cip1), PCNA, pRb(Ser249/Thr252) and TK-1, and increases intimal thickening. YY1 binds Sp1 and prevents its occupancy of a distinct element in the p21(WAF1/Cip1) promoter without YY1 itself binding the promoter. Additionally, YY1 induces ubiquitination and proteasome-dependent degradation of p53, decreasing p53 immunoreactivity in the artery wall. These findings define a new role for YY1 as both an inducer of p53 instability in smooth muscle cells, and an indirect repressor of p21(WAF1/Cip1) transcription, p21(WAF1/Cip1)-cdk4-cyclin D1 assembly and intimal thickening.

Expression of somatostatin receptors in splanchnic blood vessels of normal and cirrhotic rats

Somatostatin has been used for over two decades to treat acute variceal bleeding. Although it is assumed that somatostatin lowers portal pressure by constriction of the splanchnic arteries, little is known about the expression of somatostatin receptors (SSTR) in splanchnic blood vessels. In this study we investigated SSTR expression in splanchnic blood vessels from normal and cirrhotic rats. Cirrhosis was induced by intraperitoneal injection of 50 mg thioacetamide twice a week for 14 weeks. In portal vein, mesenteric artery and aorta of normal and cirrhotic rats, mRNA for the five known SSTR was measured by quantitative reverse transcriptase-polymerase chain reaction. SSTR subtypes 1, 2, 3 and 4 were expressed, but subtype 5 was undetectable. In the portal vein of cirrhotic animals, SSTR1 was significantly down-regulated as compared with controls. Otherwise, no major differences in receptor expression between normal and cirrhotic animals were observed. Using immunohistochemistry, we identified all five receptors, although the staining of receptor 5 was very weak. All five SSTR are expressed in splanchnic blood vessels. Our results suggest that cirrhosis reduces expression of SSTR1 in portal vein. In other vessels, no major differences between the normal and cirrhotic state were noted.

Vasodilator effect of nicorandil on retinal blood vessels in rats

We examined the effect of nicorandil on retinal blood vessels in rats in vivo. Male Wistar rats (8 to 10 weeks old) were anaesthetised with thiobutabarbital (120 mg/kg, intraperitoneal). Fundus images were captured with a digital camera that was equipped with a special objective lens. Diameters of retinal blood vessels were measured with a personal computer. Nicorandil (1-300 microg kg(-1) min(-1), intravenous [i.v.]) increased diameters of retinal blood vessels and decreased systemic blood pressure in a dose-dependent manner. Both responses to nicorandil were attenuated by glibenclamide (20 mg/kg, i.v.), an adenosine triphosphate (ATP)-dependent K(+) (K(ATP)) channel blocker. On the other hand, indomethacin (5 mg/kg, i.v.), a cyclooxygenase inhibitor, attenuated the vasodilation of retinal blood vessels, but not depressor response, to nicorandil and sodium nitroprusside. Pinacidil (1-300 microg kg(-1) min(-1), i.v.), a K(ATP) channel opener, also dilated retinal blood vessels and decreased systemic blood pressure. The responses to pinacidil were prevented by glibenclamide, but not by indomethacin. The vasodilation of retinal arteriole, but not depressor response, to sodium nitroprusside (1-30 microg kg(-1) min(-1), i.v.), a nitric oxide donor, was attenuated by indomethacin. These results suggest that nicorandil dilates retinal blood vessels through opening of K(ATP) channels and production of prostaglandins that are probably generated by nitric oxide.

Catechin combined with vitamins C and E ameliorates insulin resistance (IR) and atherosclerotic changes in aged rats with chronic renal failure (CRF)

Aging is an inevitable biological process associated with increased oxidative stress and accumulation of asymmetric dimethylarginine (ADMA) a known endogenous inhibitor of nitric oxide synthase. Atherosclerosis and IR constitute major risk factors for cardiovascular mortality in elderly with chronic kidney disease (CKD). We investigated the impact of catechin, vitamins E and C supplementation on insulin sensitivity, redox state, ADMA, nitrate and nitrite (NO 2 −/NO 3 −) levels and histological picture of heart and large blood vessels of aged rats with CRF. Findings of the present study revealed that aging in rats is associated with hyperinsulinemia, hyperlipidemia, IR indicated by higher homeostasis model assessment (HOMA)-index, increased lipid peroxidation product malondialdehyde (MDA), ADMA, and blood pressure (BP), but decreased antioxidant capacity and NO 2 −/NO 3 − levels. CRF exaggerated all these findings and caused thickened intima of carotid arteries and myocardial hypertrophy. Treatment with catechin, vitamins E and C increases the antioxidant capacity and NO 2 −/NO 3 − production but, decreases MDA, ADMA and BP levels. Also it keeps insulin sensitivity and normal intima/media thickness of carotid arteries. We conclude that decreased nitric oxide (NO) availability due to ADMA accumulation may be responsible for IR and associated atherosclerotic changes in aged rats with CRF. Catechin, vitamins E and C supplementation may moderate oxidative stress of renal failure, prevent ADMA accumulation, and counteract IR and atherosclerotic changes in the elderly.

Intestinal First-Pass Metabolism via Carboxylesterase in Rat Jejunum and Ileum

To determine the activity of a major intestinal esterase in the first-pass hydrolysis of O-isovaleryl-propranolol (isovaleryl-PL), a model ester compound, rat intestinal jejunum and blood vessels were perfused simultaneously after inhibition of a carboxylesterase (CES) by bis-p-nitrophenyl phosphate (BNPP). BNPP specifically inhibits approximately 90% of CES activity without influencing aminopeptidase activity or the transport of L-leucyl-p-nitroanilide and p-nitroaniline, nonester compounds. When isovaleryl-PL was perfused into the jejunal lumen after BNPP treatment, its absorption clearance (7.60 +/- 0.74 microl/min) increased approximately 3-fold compared with control, whereas its degradation clearance (32.5 +/- 5.40 microl/min) decreased to 23% of control. Therefore, CES seems to be mainly responsible for the intestinal first-pass hydrolysis of isovaleryl-PL. This finding is consistent with the results from studies of in vitro BNPP inhibition in the mucosal S9 fraction. V(max) values for valeryl-PL, isovaleryl-PL, and p-nitrophenyl acetate in the jejunal S9 fraction were 1.7- to 2.5-fold higher than that in the ileal S9 fraction, which agreed with the jejunum/ileum ratio (approximately 1.5-fold) of mRNA expression levels for the CES2 isozymes, AB010635 and AY034877. These findings indicated that CESs expressed in the intestine markedly contribute to first-pass hydrolysis in both jejunum and ileum.

Glutathione-S-Transferase Protects against Oxidative Injury of Endothelial Cell Tight Junctions

Oxidative damage of endothelial tight junction permeability is involved in the pathophysiology of a variety of vascular diseases. The authors studied the role of the antioxidant enzyme, human glutathione-S-transferase A4-4 (hGSTA4-4), in regulating expression of major molecules of tight junction in vascular endothelial cells under oxidative stress induced by H(2)O(2). A vascular endothelial cell line, mouse pancreatic endothelial cells (MS1), was transduced with recombinant adenoviral vector containing hGSTA4-4 gene. hGSTA4-4 induced expression of tight junction proteins occludin and zonula occludens (ZO)-1 under oxidative stress. Increased hGSTA4-4 expression correlated with increased transepithelial electrical resistance and decreased tyrosine phosphorylation of occludin and ZO-1 following exposure to H(2)O(2). In addition, morphologic dissociation of occludin, ZO-1, and F-actin during oxidative stress was reduced in hGSTA4-4-expressing cells. To explore a genetic approach for vascular diseases associated with disruption of tight junction proteins, we introduced the same viral vector to blood vessels of mice, rats, and rabbits ex vivo and found strong expression of hGSTA4-4 in endothelial cells. These results demonstrate that oxidative stress mediated disruption of tight junctions in endothelial cells may be attenuated by hGSTA4-4 expression.

Fast full-view photoacoustic imaging by combined scanning with a linear transducer array

We present a fast full-view photoacoustic imaging system for visualizing tissue structures using a linear transducer array with combined scan. In this system, a 128-element linear transducer array was used to detect photoacoustic signals by combined scanning of electronic scan and mechanical scan. An improved limited-field filtered back projection algorithm with directivity factors was applied to reconstruct the optical absorption distribution. The experiments of phantoms and in vivo blood vessels in a rat brain were performed with this system. And a clear view of the curve boundaries of objects and the network of blood vessels of rat's brain were acquired. The experimental results demonstrate the multi-element photoacoustic imaging system has the ability of imaging complicated structures of objects.

Potentiation by neuropeptide Y of histamine H 1 receptor-mediated contraction in rat blood vessels

Histamine-induced contraction and its potentiation by neuropeptide Y were investigated in rat blood vessels. Rat arteries and veins constricted with single concentrations of histamine dose-dependently (0.1–100 μM). This histamine-induced contraction immediately desensitized. Histamine H 1 receptor antagonists, 1 μM mepyramine and 1 μM diphenhydramine, abolished this transient contraction completely, whereas cimethidine, phentolamine, reserpine and tetrodotoxin failed to inhibit the contraction. Histamine H 1 receptor mRNA level by reverse transcription-polymerase chain reaction was quite parallel to histamine H 1 receptor-mediated contraction, indicating that the contraction is mediated through histamine H 1 receptors in the smooth muscle. Neuropeptide Y (10 nM in arteries and 3 nM in veins, respectively) significantly potentiated histamine H 1 receptor-mediated contraction via neuropeptide Y 1 receptors in most of rat blood vessels. Since the phospholipase C inhibitors, neomycin (1 mM) and 2-nitro-4-carboxyphenyl- N, N-diphenylcarbamate (NCDC, 10 μM), respectively, specifically abolished the potentiation, the potentiation by neuropeptide Y may depend on activation of phospholipase C.