Biomedical subjects

C Xue

Publications and source records attributed to C Xue.

At least 37 records · Page 2Linked to original sources

PubMed1999

[Humoral immune response in mice to hybrid nucleic acid vaccines containing Plasmodium falciparum merozoite surface protein 1 block 17-based gene].

AIM: To analyse the humoral immune response in mice to nucleic acid vaccines (VR1012/HG-MSP1-17 for intracellular expression or VR1012/TPA/HG-MSP-17 for secretion) containing Plasmodium falciparum merozoite surface protein 1 (MSP1) 17 block gene and gene fragment of several T cell epitopes from MSA1, MSA2, RESA, IL-1 and TT. METHODS: BALB/c or C57BL/6 mice received three times intramuscular immunization with 200 micrograms/100 microliters or 100 micrograms/100 microliters of VR1012/HG-MSP1-17 or VR1012/TPA/HG-MSP1-17 per mouse each time. Anti-HG or anti-MSP1-17 antibodies were monitored by indirect ELISA. RESULTS: BALB/c and C57BL/6 mice immunized with 100 micrograms/100 microliters of VR1012/HG-MSP1-17 per mouse raised significantly anti-HG and anti-MSP1-17 antibodies, but the levels of antibodies were not high. BALB/c mice immunized with 200 micrograms/100 microliters of VR1012/HG-MSP1-17 per mouse raised higher anti-HG antibodies but not anti-MSP1-17 antibodies. BALB/c mice immunized with 200 micrograms/100 microliters of VR1012/TPA/HG-MSP1-17 per mouse raised low level of anti-HG antibodies only. CONCLUSION: VR1012/HG-MSP1-17 is more immunogenic than VR1012/TPA/HG-MSP1-17.

Animals↗

PubMed1998

Developmental expression and localization of the catalytic subunit of protein phosphatase 2A in rat lung.

Protein phosphatase type-2A (PP2A) is a highly conserved serine/threonine phosphatase known to play a key role in cell proliferation and differentiation in vitro, but the role of PP2A in mammalian embryogenesis remains unexplored. No particular information exists as to the tissue or cell specific expression of PP2A or the relevance of PP2A expression to mammalian development in vivo. To examine expression of PP2A during mammalian lung development, we studied fetal rats from day 14 of gestation (the lung bud is formed on day 12 of gestation) to parturition. Western analysis with a specific PP2A catalytic subunit antibody identified a single 36 kDa protein, with protein levels two-fold higher in the 17 and 19 day embryonic lung as compared to the adult. With in situ hybridization and immunohistochemistry, both mRNA and protein for PP2A were localized equally to the epithelial lining of the embryonic lung airway and the surrounding mesenchyme in the 14 day embryonic lung. With maturation of the lung, PP2A becomes highly expressed in respiratory epithelium. The highest level of expression was in the earliest developing airways with columnar epithelium (the pseudoglandular stage, 15-18 days of gestation). There was a decrease in expression with the transformation to cuboidal epithelium by day 20 of gestation. This was most noticeable in the developing bronchial epithelium of the 19 and 20 day gestation lungs where only an occasional cell continues to express PP2A. Mesenchymal hybridization was most obvious in early endothelial cells of forming vascular channels at 17-19 days of gestation. PP2A respiratory epithelial expression mimicked the centrifugal development of the respiratory tree where the highest expression was in the peripheral columnar epithelium (15-18 days gestation) with only an occasional central bronchiolar cell continuing to express PP2A at 19 and 20 days gestation. Endothelial hybridization decreased with muscularization of large pulmonary arteries with low levels of expression detected in bronchial or vascular smooth muscle. In the newborn lung PP2A expression was decreased, but detectable in alveolar epithelium and vascular endothelium. In summary; 1) PP2A mRNA and protein exhibit cell specific expression during rat lung development; 2) PP2A is highly expressed in the respiratory epithelium of the fetal rat lung and is temporally related to the maturation of the bronchial epithelium; 3) and the PP2A subunit is highly expressed in early vascular endothelium, but not smooth muscle of the rat lung.

Animals↗

PubMed1998

eNOS expression is not altered in pulmonary vascular remodeling due to increased pulmonary blood flow.

Congenital heart lesions resulting in increased pulmonary blood flow are common and if unrepaired often lead to pulmonary hypertension and heart failure. Therefore, we hypothesized that increased pulmonary blood flow without changes in pressure would result in remodeling of the pulmonary arterial wall. Furthermore, because the vasodilator nitric oxide is produced by the lung, is regulated by flow in the systemic circulation, and has been associated with the regulation of smooth muscle cell proliferation, we hypothesized that increased pulmonary blood flow would result in altered expression of endothelial nitric oxide synthase (eNOS). To study this hypothesis, 42-day-old Sprague-Dawley rats had creation of an aortocaval shunt to increase pulmonary blood flow for 6 wk. The shunt resulted in a significant increase in the heart- and lung-to-body weight ratios (>2-fold; P < 0.05) without significant alteration of pulmonary or systemic blood pressures. Significant thickening of the pulmonary arterial medial wall developed, with increased muscularization of small (50-100 micron)- and medium (101-200 micron)-sized arteries as evidenced by alpha-actin smooth muscle staining. Proliferating cell nuclear antigen staining and bromodeoxyuridine labeling did not detect proliferating smooth muscle cells in the vascular wall. eNOS Western and Northern blot analyses and immunohistochemical staining demonstrated that eNOS protein and mRNA levels were not altered in the shunt lungs compared with sham controls. Therefore, increased pulmonary flow without increased pressure resulted in pulmonary artery medial thickening, without ongoing proliferation. Unlike chronic hypoxia-induced vascular remodeling, the pulmonary vascular remodeling resulting from increased pulmonary blood flow is not associated with changes in eNOS.

Animals↗

PubMed1998

Expression and mapping of protein phosphatase 2A alpha in the developing rat heart.

Protein phosphatase 2A (PP2A) is a second messenger involved in cell cycle regulation, cell transformation, and cell fate determination. We previously identified a gene encoding the alpha catalytic subunit of PP2A in the embryonic rat heart, but its role in cardiac morphogenesis was unknown. In this study, we examined the developmental expression of PP2A alpha mRNA and protein in the heart using Northern and Western analysis, in situ hybridization, and immumohistochemical staining. We found two major PP2A alpha transcripts in the rat heart (1.8 and 2.4 kb), at all stages examined. By Western blotting, PP2A alpha protein levels were twice as high in the embryonic rat heart compared with the adult. In situ hybridization on embryonic d 12 showed that PP2A alpha mRNA was expressed in the heart, brain, tail, and limb buds. Cardiac PP2A alpha expression was regionally restricted to the atrium, ventricle, and truncus arteriosus. PP2A alpha expression did not extend into the more distal aortic sac or aortic arches. Cross-sectional hybridization revealed PP2A alpha mRNA in the epicardium, pericardium, and endothelium. Later in development, mRNA expression was also detected at high levels in mesenchymal cells populating the endocardial cushions and in myocardium. At term, PP2A alpha was highly expressed in endothelial cells, but not in the underlying myocardium. PP2A alpha protein had a similar distribution at all embryonic stages examined. These results show that there is transcriptional, translational, and cell-specific regulation of PP2A alpha during heart development. We speculate on the role of PP2A alpha-mediated dephosphorylation in cardiac morphogenesis and suggest a number of possible molecular targets.

Animals↗

PubMed1998

Antioxidative activity of carp blood plasma on lipid peroxidation.

Antioxidative activity of carp blood plasma was estimated by measuring hydroperoxides formed by liposome peroxidation during the exposure of liposomes to AAPH. Ascorbic acid of high concentration, uric acid of low content, and tocopherol formed special protective system against lipid poroxidation in fish plasma. The decrease of uric acid, ascorbic acid, and tocopherol showed synergism of ascorbic acid and tocopherol, uric acid, and tocopherol. Carp blood plasma with a low concentration of protein (about 2%) and SH groups (88 microM) had a great effect on the antioxidative activity, as the effects of ascorbic acid, uric acid, and tocopherol were dramatically extended. Dialysed carp protein also displayed a very strong antioxidative activity on lipid peroxidation of a multilayer liposome system.

Adult↗

PubMed1998

Antioxidative activities of several marine polysaccharides evaluated in a phosphatidylcholine-liposomal suspension and organic solvents.

The antioxidative activities of several water-soluble marine polysaccharides, alginate (ALG), alginate sulfate (SALG), propylene glucolalginate sodium sulfate (PSS), propylene glucol mannuronate sulfate (PGMS), the oligosaccharide of chitosan (OLC), N,O-carboxymethyl chitosan (NOCC) and hydroxypropylated chitosan (HPC), were examined in a phosphatidylcholine (PC)-liposomal suspension containing the water-soluble radical emitter, 2,2'-azobis (2-amidinopropane) dihydrochloride. In the suspensions containing OLC and SALG, the initial rates of PC-OOH accumulation were 2.78 x 10(-8) MS-1 and 2.88 x 10(-8) MS-1, respectively, while all the polysaccharides tested showed antioxidative activity. Liposoluble marine polysaccharides, hexanoyl chitin (HCH) and an N-benzoylhexanoyl chitosan (NBHC) solution, also retarded the hydroperoxide accumulation of methyl linoleate by effectively trapping peroxide radicals in organic solvents when the radical chain reaction had been initiated by 2,2'-azobis (2,4-dimethylvaleronitrile). The kinetic data presented indicate that the alginate and chitin derivatives can be expected to play a role in the antioxidative mechanism of biological systems.

Alginates↗

PubMed1997

Transcriptional regulation of the HOX4C gene by basic fibroblast growth factor on rheumatoid synovial fibroblasts.

OBJECTIVE: To examine the expression of genes of the HOX D cluster in the synovial tissue of patients with rheumatoid arthritis (RA), and to determine whether basic fibroblast growth factor (bFGF) influences the expression and transcriptional regulation of the gene. METHODS: The expression of genes of the HOX D cluster, including HOX4C, HOX4D, HOX4H, and HOX4I, was determined in the synovium of 4 patients with RA and 4 with osteoarthritis (OA) by in situ reverse transcription (RT) and RT-polymerase chain reaction (RT-PCR). The induction of HOX4C messenger RNA (mRNA) by bFGF was determined by RT-PCR. The binding activity of a transcriptional regulator of the HOX4C gene, C2, was analyzed by the mobility shift assay. NIH-3T3 cells transfected with a construct containing C2 binding sequence were incubated with bFGF, and the activity of the reporter was measured by luciferase assay. RESULTS: Using an in situ RT assay, specific expression of HOX4C mRNA was detected in 3 of 4 RA synovial samples, whereas none of the OA synovia expressed HOX4C. HOX4D, HOX4H, and HOX4I genes were expressed in all synovial samples from RA and OA patients. The presence of HOX4C mRNA was also confirmed by RT-PCR and Southern blotting. Treatment with bFGF increased the expression of HOX4C mRNA in RA fibroblasts. The mobility shift assay and luciferase assay showed that bFGF enhanced C2 binding activity and significantly increased the transcriptional activity on RA fibroblasts. CONCLUSION: Our findings suggest that HOX4C is involved in synovial hyperplasia, and that the transcriptional regulation of HOX4C genes by bFGF may play a crucial role in the pathogenesis of RA.

Arthritis, Rheumatoid↗

PubMed1997

Characterisation of fibroblast-like cells in pannus lesions of patients with rheumatoid arthritis sharing properties of fibroblasts and chondrocytes.

OBJECTIVE: To better understand the characteristics of synoviocytes located in the rheumatoid arthritis (RA) pannus. METHODS: One cell line, termed PSC, was cloned from RA pannus lesions. Phenotypic analysis was done by contrast microscopy, indirect immunostaining, and safranin O staining. Transcription of several protooncogenes and matrix degrading enzymes was evaluated. The expression of mRNA for collagen II was detected by in situ hybridisation. The ability of anchorage independent growth was assessed by soft agarose culture. RESULTS: PSCs showed a high transcription of protooncogenes c-fos, c-myc and c-jun. They also expressed mRNA for matrix degrading enzymes, such as collagenase, cathepsin B, and cathepsin L. Anchorage independent growth assay demonstrated that PSCs formed colonies in soft agar culture. Phenotypic analysis showed that this fibroblast-like PSC was stained intensely with anti-vimentin and anti-fibroblast antibody. In situ reverse transcriptase assay showed that the cell line expressed type II collagen mRNA. CONCLUSION: Alternative fibroblast-like cells were identified in the pannus lesion of RA sharing properties of fibroblasts and chondrocytes. These findings suggest that this fibroblast-like cell derived from pannus lesions may contribute to the destruction of the cartilage in RA.

Aged↗

PubMed1997

[Study on standard of patch test for cosmetic allergens].

39 allergens, chemical ingredients commonly used in cosmetics in China, were tested. The safe concentration of allergens was determined in experiments on animals. On the basis of the above results and referring to the literature, the concentration of allergens used in patch test for human was designed and the patch test was carried out on 10 volunteers by routine method. Finally the concentration which gave no reaction in all 10 volunteers was verified in patients with eczema or contact dermatitis. The rate of positive reactions for each allergen was raged from 0 to 12% with an average 3.4%, According to the results of three above mentioned experiments the series of allergen standards for patch test was established. It is used as an appendix to the document for diagnostic criteria and principles of management of consmetic diseases.

Allergens↗

PubMed1997

[Study on the contact allergen in 720 patients with dermatitis and eczema].

In order to investigate the causative factors of dermatitis and eczema, patch test was performed using the GB7804-87 standard allergens in 720 patients with dermatitis and eczema. There were 376 patients reacted to one or more allergens. The total positive reaction rate was 52.2%. Positive reactions were most frequently with cobaltsulphate (118 cases, 16.4%), potassium dichromate (115 cases, 16.0%), nickelchloride (108 cases, 15.0%) mercuric chloride (106 cases, 14.7%), Beihai detergent powder (63 cases, 8.8%), and p-phenylene diamine (50 cases, 6.9%). The positive rate was above 1% in 18 allergens. This study shows that the standard screening allergens are valuable in the investigation of the aetiology of the dermatitis and eczema.

Adolescent↗

PubMed1997

[The effect of blood-pancreatic juice barrier on antitumor drugs excretion].

Chemotherapy is one of important adjuvant therapies for patients with pancreatic adenocarcinoma, but the mechamism 5-FU and MMC distributed over the pancreas is not known at home and abroad. Based on determining the ratio of the concentration of several kinds of antibioticsin plasma and pancreatic juice, we used fourteen dogs to study the distribution and the relationship of agents in plasma and pancreatic juice after giving 5-FU and MMC intravenously. At the same time, we observed some patients who received Whipple's operation. The results showed that 5-FU and MMC in plasma can penetrate the pancreatic tissue and cross the blood-pancreatic juice barrier (BPJB). Both agents suitable for the adjuvant chemotherapy of pancreatic adenocarcinoma.

Ampulla of Vater↗

PubMed1996

Induction of nitric oxide synthase in the human cardiac allograft is associated with contractile dysfunction of the left ventricle.

BACKGROUND: The mechanisms underlying cardiac contractile dysfunction after transplantation remain poorly defined. Previous work has revealed that inducible nitric oxide synthase (iNOS) is expressed in the rat heterotopic cardiac allograft during rejection; resultant overproduction of nitric oxide (NO) might cause cardiac contractile dysfunction via the negative inotropic and cytotoxic actions of NO. In this investigation, we tested the hypothesis that induction of iNOS may occur and be associated with cardiac allograft contractile dysfunction in humans. METHODS AND RESULTS: We prospectively studied 16 patients in the first year after cardiac transplantation at the time of serial surveillance endomyocardial biopsy. Clinical data, the results of biopsy histology, and echocardiographic and Doppler evaluation of left ventricular systolic and diastolic function were recorded. Total RNA was extracted from biopsy specimens, and mRNA for beta-actin, detected by reverse transcription-polymerase chain reaction (RT-PCR) using human specific primers, was used as a constitutive gene control; iNOS mRNA was similarly detected by RT-PCR using human specific primers. iNOS protein was detected in biopsy frozen sections by immunofluorescence. Myocardial cGMP was measured by radioimmunoassay, and serum nitrogen oxide levels (NOx = NO2 + NO3) were measured by chemiluminescence. iNOS mRNA was detected in allograft myocardium at some point in each patient and in 59 of 123 biopsies (48%) overall. In individual patients, iNOS mRNA expression was episodic and time dependent; the frequency of expression was highest during the first 180 days after transplant (P = .0006). iNOS protein associated with iNOS mRNA was detected by immunofluorescence in cardiac myocytes. iNOS mRNA expression was not related to the ISHLT histological grade of rejection or to serum levels of NOx but was associated with increased levels of myocardial cGMP (P = .01) and with both systolic (P = .024) and diastolic (P = .006) left ventricular contractile dysfunction measured by echocardiography and Doppler. CONCLUSIONS: These data support a relation between iNOS mRNA expression and contractile dysfunction in the human cardiac allograft.

Adolescent↗

PubMed1996

Expression of nitric oxide synthase in mucosal cells of the canine colon.

The expression of nitric oxide synthase (NOS) in the mucosa of the canine colon was investigated with in situ hybridzation, immunohistochemistry (using isoform specific antibodies), western analysis, and NADPH diaphorase (NADPH-d) histochemistry. In situ hybridization using a common probe for known isoforms of NOS showed that NOS mRNA was strongly expressed in mucosal cells. A gradient in the degree of hybridization was noted from the base of the crypts to the luminal surface. This gradient was also apparent using an endothelial NOS (eNOS)-specific probe. Neural NOS-like immunoreactivity (nNOS-LI) was observed in columnar epithelial cells, and the same population of cells was stained with NADPH-d. Endothelial NOS-like immunoreactivity (eNOS-LI) was also found in mucosal cells; however, this eNOS-LI was confined to mucous cells. These cells were not stained with NADPH-d. The existence of eNOS in mucosal cells was confirmed by in situ hybridization using the probe which specifically hybridized with mRNA of eNOS and by western blots which demonstrated the expression of a 135-kDa protein in mucosal homogenates. The differential expression of NOS isoforms and the gradient in expression along the length of the crypts suggest complex roles for NO in the development of colonic epithelial cells and in secretion and transport functions of the colonic mucosa.

Animals↗

PubMed1996

L-arabinose selectively inhibits intestinal sucrase in an uncompetitive manner and suppresses glycemic response after sucrose ingestion in animals.

The objective of this study was to investigate the effects of L-arabinose on intestinal alpha-glucosidase activities in vitro and to evaluate its effects on postprandial glycemic responses in vivo. L-Arabinose inhibited the sucrase activity of intestinal mucosa in an uncompetitive manner (Ki, 2 mmol/L). Neither the optical isomer D-arabinose nor the disaccharide L-arabinobiose inhibited sucrase activity, whereas D-xylose was as potent as L-arabinose in inhibiting this activity. L-Arabinose and D-xylose showed no inhibitory effect on the activities of intestinal maltase, isomaltase, trehalase, lactase, and glucoamylase, or pancreatic amylase. In contrast, a known alpha-glucosidase inhibitor, acarbose, competitively inhibited (Ki, 1.1 mumol/L) sucrase activity and also inhibited intestinal maltase, glucoamylase, and pancreatic amylase. L-Arabinose suppressed the increase of blood glucose after sucrose loading dose-dependently in mice (ED50, 35 mg/kg), but showed no effect after starch loading. The suppressive effect of D-xylose on the increase of blood glucose after sucrose loading was 2.4 times less than that of L-arabinose, probably due to intestinal absorption of the former. Acarbose strongly suppressed glycemic responses in both sucrose loading (ED50, 1.1 mg/kg) and starch loading (ED50, 1.7 mg/kg) in mice. L-Arabinose suppressed the increase of plasma glucose and insulin in rats after sucrose loading, the suppression of the former being uninterruptedly observed in mice for 3 weeks. Thus, the results demonstrated that L-arabinose selectively inhibits intestinal sucrase activity in an uncompetitive manner and suppresses the glycemic response after sucrose ingestion by inhibition of sucrase activity.

Acarbose↗

PubMed1996

Chronic hypoxia upregulates endothelial and inducible NO synthase gene and protein expression in rat lung.

The effect of chronic hypoxia-induced pulmonary hypertension on nitric oxide synthase (NOS) in the lung is controversial. To clarify the regulation of endothelial and inducible NOS (eNOS and iNOS) expression in the chronically hypoxic lung, Northern and Western blot analyses were performed on mRNA and total protein from lungs of rats exposed to 3 wk of hypoxia (10% O2, normobaric) or normoxia. Expression of the mRNA and protein for eNOS was significantly increased (1.6-fold and 2.1-fold, respectively) by hypoxia. Immunohistochemistry with an isoform-specific antibody demonstrated de novo expression of eNOS in the endothelium of resistance vessels in the pulmonary vasculature of the hypoxic rats. eNOS was detected in the endothelium of large vessels in both normoxic and hypoxic rat lungs. The level of mRNA and protein for iNOS was also found to be significantly increased (1.9-fold and 1.4-fold, respectively). In addition to the 4.4-kilobase (kb) iNOS mRNA species, a novel 4.0-kb species was also induced by hypoxia. We conclude that expression of eNOS and iNOS was increased in the lungs of rats subjected to chronic hypoxia, and that there was de novo expression of eNOS protein in the microvascular endothelium.

Animals↗

PubMed1996

Developmental expression of NOS isoforms in fetal rat lung: implications for transitional circulation and pulmonary angiogenesis.

To better understand the role of nitric oxide (NO) in fetal lung development, specifically in the transition of the fetal circulation at birth, we studied the timing of cell-specific expression of NO synthase (NOS) isoforms from formation of lung buds (13th day of gestation) to 7 days postnatal. Expression of NOS was studied using immunohistochemical labeling with antibodies against the three known NOS isoforms and the NADPH diaphorase technique (NADPH-d). Endothelial NOS (eNOS) immunoreactivity was found in the cells of the 14-day fetal lung. As gestation proceeded, the quantity of these immunopositive cells increased, and they coalesced to form an inner (endothelial) layer of pulmonary vessels. This process of angiogenesis marked by eNOS-positive cells was seen from 15 days of gestation to at least 7 days postnatal. A majority of the eNOS immunoreactivity appeared densely in one focal spot in the cytoplasm, indicating that during development the eNOS may be primarily located in a cytoplasmic organelle. Epithelial cells of the rat airway from the same developmental period were positively stained with both brain NOS antibody (bNOS) and NADPH-d at the beginning of 13 days of gestation. Then the intensity of stainings began to decrease and reached the lowest level in the 16-day fetal lung. However, the NOS stainings of the epithelium, especially in small canalicular structures of the airways, began to increase at 18 days of gestation and was dramatically elevated at 20 days of gestation (term is 22 days). Postnatally, NOS in epithelium was decreased in distal airways in conjunction with the formation of alveolar structure. Inducible NOS (iNOS) immunoreactivity was also found in the epithelium of rat lung airways after 16 days of gestation. Unlike the bNOS staining, iNOS immunoreactivity exhibited a pattern of a small dot-like staining within epithelial cytoplasm during gestation and the first day postnatal, then changed to a pattern of diffuse cytoplasmic staining by the 7th postnatal day. This study concludes that 1) expression of three isoforms of NOS is present and regulated during lung development; 2) markedly increased NOS in epithelium near term supports a role for NO in mediating the pulmonary transition from fetal to neonatal life; and 3) eNOS immunohistochemistry serves as an effective marker to follow the process of pulmonary angiogenesis and suggests the concept of in situ formation of endothelial vesicles in developing mesenchyme.

Aging↗

PubMed1996

Chronic inhaled nitric oxide: effects on pulmonary vascular endothelial function and pathology in rats.

Nitric oxide (NO) is a potent endogenous vasodilator produced in endothelial cells. Inhaled NO selectively vasodilates the pulmonary circulation. We determined the effects of chronic inhaled NO on hypoxic pulmonary vascular remodeling and endothelium NO-dependent and -independent vasodilation during normoxic and hypoxic conditions in rats. Rats were exposed to 3 wk of normoxia (N), normoxia + 20 ppm inhaled NO (N+NO), chronic hypoxia with 10% normobaric oxygen (CH), or CH and 20 ppm inhaled NO (CH+NO). Inhaled NO decreased the number of muscular pulmonary arteries, the medial smooth muscle thickness, and the right ventricular hypertrophy associated with chronic hypoxia but had no effect on these parameters in normoxic rats. All groups were evaluated with isolated perfused lungs. The pulmonary artery pressure increased by the same amount in the CH and CH+NO rats compared with N rats. Inhibition of NO synthase with N omega-nitro-L-arginine methyl ester (L-NAME) caused greater pulmonary vasoconstriction in CH (19.2 +/- 3.7 mmHg) vs. N (7.8 +/- 3.0 mmHg) and less in CH+NO (9.1 +/- 0.8 mmHg) vs. CH rats. Bradykinin (3 micrograms) caused greater vasodilation in CH (76 +/- 12%) vs. N (29 +/- 5%) but significantly less in CH+NO (41 +/- 11%) vs. CH rats. Vasodilation with acute inhaled NO (40 ppm) was no different in CH vs. N rats but was lower in CH+NO (19 +/- 5%) vs. CH (34 +/- 6%) rats. This study demonstrates that chronic inhaled NO attenuates hypoxic pulmonary vascular remodeling. Furthermore, these results suggest that chronic inhaled NO decreases endothelium NO-dependent and -independent vasodilation.

Administration, Inhalation↗

PubMed1996

Upregulation of nitric oxide synthase correlates temporally with onset of pulmonary vascular remodeling in the hypoxic rat.

Alterations in nitric oxide signaling have been hypothesized to have an etiologic role in the development of hypoxic pulmonary hypertension. However, changes in the expression of nitric oxide synthase (NOS) in hypoxic lungs remains controversial. In this study, we used (1) Northern and Western analyses to measure NOS mRNA and protein expressions, (2) lung histology together with measurements of lung and heart weights to monitor pulmonary vascular remodeling, and (3) immunohistochemistry to localize NOS proteins. The data demonstrated that endothelial NOS mRNA and protein were upregulated over 1 to 7 days of hypoxia that temporally correlated with and preceded the vascular remodeling that occurred in the course of the development of hypoxic pulmonary hypertension. Hypoxia also induced brain NOS in bronchial epithelium and inducible NOS in vascular smooth muscle but did not affect inducible NOS expression in macrophages or basal guanylyl cyclase activity in the lung. These findings showed that upregulation of endothelial NOS was tightly correlated with the vascular remodeling induced by hypoxia, suggesting a role for nitric oxide in the development of pulmonary hypertension.

Animals↗