Biomedical subjects

W Ni

Publications and source records attributed to W Ni.

At least 19 recordsLinked to original sources

PubMed2001

Antiinflammatory and antiarteriosclerotic actions of HMG-CoA reductase inhibitors in a rat model of chronic inhibition of nitric oxide synthesis.

Recent studies suggest that some of the beneficial effects of 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may be due to their cholesterol-lowering independent effects on the blood vessels. Chronic inhibition of endothelial nitric oxide (NO) synthesis by oral administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) to rats induces early vascular inflammation as well as subsequent arteriosclerosis. The aim of the study is to test whether treatment with statins attenuates such arteriosclerotic changes through their cholesterol-lowering independent effects. We investigated the effect of statins (pravastatin and cerivastatin) on the arteriosclerotic changes in the rat model. We found that treatment with statins did not affect serum lipid levels but markedly inhibited the L-NAME-induced vascular inflammation and arteriosclerosis. Treatment with statins augmented endothelial NO synthase activity in L-NAME-treated rats. We also found the L-NAME induced increase in Rho membrane translocation in hearts and its prevention by statins. Such vasculoprotective effects of statins were suppressed by the higher dose of L-NAME. In summary, in this study, we found that statins such as pravastatin and cerivastatin inhibited vascular inflammation and arteriosclerosis through their lipid-lowering independent actions in this model. Such antiarteriosclerotic effects may involve the increase in endothelial NO synthase activity and the inhibition of Rho activity.

Animals↗

PubMed2001

New anti-monocyte chemoattractant protein-1 gene therapy attenuates atherosclerosis in apolipoprotein E-knockout mice.

BACKGROUND: Monocyte recruitment into the arterial wall and its activation may be the central event in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine for monocyte recruitment, and its receptor (CCR2) may mediate such in vivo response. Although the importance of the MCP-1/CCR2 pathway in atherogenesis has been clarified, it remains unanswered whether postnatal blockade of the MCP-1 signals could be a unique site-specific gene therapy. METHODS AND RESULTS: We devised a new strategy for anti-MCP-1 gene therapy to treat atherosclerosis by transfecting an N-terminal deletion mutant of the human MCP-1 gene into a remote organ (skeletal muscle) in apolipoprotein E-knockout mice. This strategy effectively blocked MCP-1 activity and inhibited the formation of atherosclerotic lesions but had no effect on serum lipid concentrations. Furthermore, this strategy increased the lesional extracellular matrix content. CONCLUSIONS: We conclude that this anti-MCP-1 gene therapy may serve not only to reduce atherogenesis but also to stabilize vulnerable atheromatous plaques. This strategy may be a useful and feasible form of gene therapy against atherosclerosis in humans.

Animals↗

PubMed2001

HIV-1 Tat neurotoxicity is prevented by matrix metalloproteinase inhibitors.

The release of potentially neurotoxic molecules by HIV-infected brain macrophages is accompanied by neuronal injury and death that results in the development of HIV-associated dementia (HAD). Among the potential neurotoxins implicated in the development of HAD is the HIV-1 transactivating protein, Tat. To investigate the mechanism by which Tat causes neurotoxicity, brain-derived Tat sequences from nondemented (Tat-ND) and demented (Tat-HAD) AIDS patients, which differed primarily in the augmenting region of Tat, were expressed in U937 monoblastoid cells and primary human macrophages. Cells expressing Tat-HAD protein exhibited elevated matrix metalloproteinase (MMP)-2 and -7 release and activation, but cells expressing Tat-ND did not exhibit enhanced MMP expression. Conditioned media from Tat-HAD-transfected cells caused significantly greater neuronal death (15.4 +/- 4.3%) than did Tat-ND (4.4 +/- 2.1%) or nontransfected (2.1 +/- 0.8%) cell-derived conditioned media. The neurotoxicity induced by Tat-HAD was inhibited by anti-MMP-2 or -7 antibodies (p < 0.005) but not by antibodies against MMP-9 or Tat. Similarly, scid/nod mice receiving striatal implants of Tat-HAD-transfected cells exhibited greater neurobehavioral abnormalities and neuronal loss (p < 0.005) than did animals receiving Tat-ND or nontransfected cells, which were reduced by treatment with the MMP inhibitor prinomastat (p < 0.005). These findings indicate that Tat causes neuronal death through an indirect mechanism that is Tat sequence dependent and involves the induction of MMPs.

AIDS Dementia Complex↗

PubMed2001

Grammatism.

Findings from the literature on language development, dyslexia, and adult sentence processing provide a vehicle for comparing two models of the symptom complex associated with agrammatism. One model contends that agrammatism represents a deficit in linguistic structures. The other model maintains that the linguistic behavior associated with agrammatism is the result of a limitation in language processing. To adjudicate between the models, the present paper examines one linguistic construction, the restrictive relative clause. The results of experimental investigations across several subject populations reveal parallel patterns of linguistic behavior on this construction. The findings favor the processing limitation account of the linguistic difficulties experienced by agrammatic aphasics in comprehending sentences with a restrictive relative clause.

Aphasia, Broca↗

PubMed2001

Antisense oligodeoxynucleotide inhibition of tumor necrosis factor-alpha expression is neuroprotective after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) expression is increased in brain after cerebral ischemia, although little is known about its abundance and role in intracerebral hemorrhage (ICH). A TNF-alpha-specific antisense oligodeoxynucleotide (ORF4-PE) was used to study the extent to which TNF-alpha expression influenced neurobehavioral outcomes and brain damage in a collagenase-induced ICH model in rat. METHODS: Male Sprague-Dawley rats were anesthetized, and ICH was induced by intrastriatal administration of heparin and collagenase. Immediately before or 3 hours after ICH induction, ORF4-PE was administered directly into the site of ICH. TNF-alpha mRNA and protein levels were measured by reverse transcriptase-polymerase chain reaction and immunoblot analyses. Cell death was measured by terminal deoxynucleotidyl transferase-mediated uridine 5'triphosphate-biotin nick end labeling (TUNEL). Neurobehavioral deficits were measured for 4 weeks after ICH. RESULTS: ICH induction (n=6) elevated TNF-alpha mRNA and protein levels (P:<0.01) at 24 hours after the onset of injury compared with sham controls (n=6). Immunohistochemical labeling indicated that ICH was accompanied by elevated expression of TNF-alpha in neutrophils, macrophages, and microglia. Administration of ORF4-PE (2.0 nmol) directly into striatal parenchyma, 15 minutes before (n=4) or 3 hours after (n=6) ICH, decreased levels of TNF-alpha mRNA (P:<0.001) and protein (P:<0. 01) in the brain tissue surrounding the hematoma compared with animals treated with saline alone (n=6). Mean+/-SEM striatal cell death (cells per high-powered field) was also reduced in animals receiving ORF4-PE (34.1+/-5.0) compared with the saline-treated ICH group (80.3+/-7.50) (P:<0.001). ORF4-PE treatment improved neurobehavioral deficits observed at 24 hours (P:<0.001) after induction of ICH (n=6) compared with the untreated ICH group (n=6). This improvement was maintained at 28 days after hemorrhage induction (P:<0.001). CONCLUSIONS: These results indicate a pathogenic role for TNF-alpha during ICH and demonstrate that reducing TNF-alpha expression using antisense oligodeoxynucleotides is neuroprotective.

Animals↗

PubMed2000

Role of monocyte chemoattractant protein-1 in cardiovascular remodeling induced by chronic blockade of nitric oxide synthesis.

BACKGROUND: Chronic inhibition of endothelial nitric oxide (NO) synthesis by the administration of N:(omega)-nitro-L-arginine methyl ester (L-NAME) to rats induces early vascular inflammatory changes (monocyte infiltration into coronary vessels and monocyte chemoattractant protein-1 [MCP-1] expression) as well as subsequent arteriosclerosis (medial thickening and perivascular fibrosis) and cardiac fibrosis. However, the role of MCP-1 in this process is not known. METHODS AND RESULTS: We investigated the effect of a specific monoclonal anti-MCP-1 neutralizing antibody in rats treated with L-NAME to determine the role of monocytes in the regulation of cardiovascular remodeling. We found increased expression of MCP-1 mRNA in vascular endothelial cells and monocytes in inflammatory lesions. Cotreatment with an anti-MCP-1 antibody, but not with control IgG, prevented the L-NAME-induced early inflammation and reduced late coronary vascular medial thickening. In contrast, the anti-MCP-1 antibody did not decrease the development of perivascular fibrosis, the expression of transforming growth factor (TGF)-beta(1) mRNA, or systolic pressure overload induced by L-NAME administration. CONCLUSIONS: These results suggest that MCP-1 is necessary for the development of medial thickening as well as monocyte recruitment. In contrast, the pathogenesis of fibrosis may involve other factors, such as TGF-beta(1).

Animals↗

PubMed2000

AIDS- and non-AIDS-related PML association with distinct p53 polymorphism.

A population-based analysis of progressive multifocal leukoencephalopathy (PML) showed PML frequencies of 5.1% among patients with AIDS and 0.07% among patients with hematologic malignancies, but similar clinical features of PML in both groups. Sequencing of the p53 gene, exon 4, showed heterozygosity (Arg-Pro) at codon 72 in five of six PML patients. These findings indicate that frequencies of non-AIDS- and AIDS-related PML differ markedly but p53 polymorphisms may influence the occurrence of PML in both groups.

Acquired Immunodeficiency Syndrome↗

PubMed2000

The diagnosis value and its implication of impulse oscillometry in obstructive sleep apnea syndrome patients.

The change of measurements of impulse oscillometry (IOS) in obstructive sleep apnea syndrome (OSAS) patients and its mechanism were observed. The respiratory impedance was measured by using IOS technique and polysomnography (PSG) was monitored synchronously in 36 OSAS patients, 14 patients with chronic obstructive pulmonary disease (COPD) and 12 normal controls. Results showed that R20 in OSAS group was significantly higher than in COPD group and control group (P < 0.01). R5-R20 in OSAS group was lower than that in COPD group, but significantly higher than that in control group (P < 0.01). The levels of R20 and R5-R20 were positively correlated with severity degree of the disease. In addition, apnea-hyponea index (AHI) was positively correlated with R5 and R20 with the correlation index (r)being 0.66 and 0.86 respectively. The lowest SO2 was negatively correlated with R5 and R5-R20, with r being -0.66 and -0.79 respectively. The mean SO2 was negatively correlated with R5 and R5-R20 with r being -0.81 and -0.69 respectively. IOS technique could be used as a valuable tool for assessing the degree of upper airway obstruction in the patients with OSAS, and could help to explore its pathological mechanism.

Adult↗

PubMed2000

Anti-monocyte chemoattractant protein-1 gene therapy inhibits vascular remodeling in rats: blockade of MCP-1 activity after intramuscular transfer of a mutant gene inhibits vascular remodeling induced by chronic blockade of NO synthesis.

Monocyte chemoattractant protein-1 (MCP-1) may play an essential part in the formation of arteriosclerosis by recruiting monocytes into the arterial wall. Thus, we devised a new strategy for anti-MCP-1 gene therapy against arteriosclerosis by transfecting an amino-terminal deletion mutant (missing the amino-terminal amino acids 2 to 8) of the human MCP-1 gene into a remote organ (skeletal muscles). Intramuscular transduction with the mutant MCP-1 gene blocked monocyte recruitment induced by a subcutaneous injection of recombinant MCP-1. In a rat model in which the chronic inhibition of endothelial nitric oxide synthesis induces early vascular inflammation as well as subsequent coronary vascular remodeling, this strategy suppressed monocyte recruitment into the coronary vessels and the development of vascular medial thickening, but did not reduce perivascular fibrosis. Thus, MCP-1 is necessary for the development of medial thickening but not for fibrosis in this model. This new strategy may be a useful and feasible gene therapy against arteriosclerosis.

Animals↗

PubMed2000

Lentivirus infection in the brain induces matrix metalloproteinase expression: role of envelope diversity.

Infection of the brain by lentiviruses, including human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV), causes inflammation and results in neurodegeneration. Molecular diversity within the lentivirus envelope gene has been implicated in the regulation of cell tropism and the host response to infection. Here, we examine the hypothesis that envelope sequence diversity modulates the expression of host molecules implicated in lentivirus-induced brain disease, including matrix metalloproteinases (MMP) and related transcription factors. Infection of primary macrophages by chimeric HIV clones containing brain-derived envelope fragments from patients with HIV-associated dementia (HAD) or nondemented AIDS patients (HIV-ND) showed that MMP-2 and -9 levels in conditioned media were significantly higher for the HAD clones. Similarly, STAT-1 and JAK-1 levels were higher in macrophages infected by HAD clones. Infections of primary feline macrophages by the neurovirulent FIV strain (V(1)CSF), the less neurovirulent strain (Petaluma), and a chimera containing the V(1)CSF envelope in a Petaluma background (FIV-Ch) revealed that MMP-2 and -9 levels were significantly higher in conditioned media from V(1)CSF- and FIV-Ch-infected macrophages, which was associated with increased intracellular STAT-1 and JAK-1 levels. The STAT-1 inhibitor fludarabine significantly reduced MMP-2 expression, but not MMP-9 expression, in FIV-infected macrophages. Analysis of MMP mRNA and protein levels in brain samples from HIV-infected persons or FIV-infected cats showed that MMP-2 and -9 levels were significantly increased in lentivirus-infected brains compared to those of uninfected controls. Elevated MMP expression was accompanied by significant increases in STAT-1 and JAK-1 mRNA and protein levels in the same brain samples. The present findings indicate that two lentiviruses, HIV and FIV, have common mechanisms of MMP-2 and -9 induction, which is modulated in part by envelope sequence diversity and the STAT-1/JAK-1 signaling pathway.

AIDS Dementia Complex↗

PubMed2000

An event-related neuroimaging study distinguishing form and content in sentence processing.

Two coordinated experiments using functional Magnetic Resonance Imaging (fMRI) investigated whether the brain represents language form (grammatical structure) separately from its meaning content (semantics). While in the scanner, 14 young, unimpaired adults listened to simple sentences that were either nonanomalous or contained a grammatical error (for example, *Trees can grew.), or a semantic anomaly (for example, *Trees can eat.). A same&frasl;different tone pitch judgment task provided a baseline that isolated brain activity associated with linguistic processing from background activity generated by attention to the task and analysis of the auditory input. Sites selectively activated by sentence processing were found in both hemispheres in inferior frontal, middle, and superior frontal, superior temporal, and temporo-parietal regions. Effects of syntactic and semantic anomalies were differentiated by some nonoverlapping areas of activation: Syntactic anomaly triggered significantly increased activity in and around Broca's area, whereas semantic anomaly activated several other sites anteriorly and posteriorly, among them Wernicke's area. These dissociations occurred when listeners were not required to attend to the anomaly. The results confirm that linguistic operations in sentence processing can be isolated from nonlinguistic operations and support the hypothesis of a specialization for syntactic processing.

Adult↗

PubMed2000

Pravastatin attenuates cardiovascular inflammatory and proliferative changes in a rat model of chronic inhibition of nitric oxide synthesis by its cholesterol-lowering independent actions.

Recent studies suggest that some of the beneficial effects of 3-hydroxyl-3-methylglutaryl (HMG)-CoA reductase inhibitors such as pravastatin may be through their cholesterol-lowering independent effects on the blood vessels. We have recently reported that chronic inhibition of nitric oxide (NO) synthesis with N(omega)nitro-L-arginine methyl ester (L-NAME) increases systolic blood pressure and induces coronary vascular inflammatory changes in rats. We designed this study to investigate whether treatment with pravastatin attenuates such proarteriosclerotic changes through their cholesterol-lowering independent effects. Several groups of Wistar-Kyoto rats were studied: the control group, L group received L-NAME in their drinking water (100 mg/kg per day) and L+Px group received L-NAME plus pravastatin (50, 100 or 250 mg/kg per day). We observed marked increases in monocyte infiltration into the coronary arteries, proliferative cell nuclear antigen-positive cells, and monocyte chemoattractant protein-1 (MCP-1) expression in the heart on day 3 after L-NAME administration began. Treatment with pravastatin did not affect serum cholesterol levels or systolic blood pressure but did reduce the L-NAME induced inflammatory and proliferative changes. Pravastatin also attenuated the MCP-1 gene expression induced by L-NAME. In summary, pravastatin inhibited the inflammatory and proliferative changes in the coronary vessels through their cholesterol-independent effects in this model, which may provide an insight into the mechanisms of anti-inflammatory or anti-arteriosclerotic actions of pravastatin.

Animals↗

PubMed1999

Paroxysmal dyskinesias in patients with HIV infection.

OBJECTIVE: To determine the clinical features of paroxysmal dyskinesias among HIV type 1 (HIV-1)-seropositive patients. BACKGROUND: Movement disorders have been associated with HIV infection, although the full spectrum of these disorders remains uncertain. METHODS: Six adult HIV-1-seropositive patients presenting with paroxysmal dyskinesias were identified. Each patient underwent metabolic, CSF, EEG, and neuroimaging studies. RESULTS: Mean age at onset was 34.5 years and five of six patients were AIDS defined. Dyskinesias were focal, multifocal, or hemidystonic in four patients and generalized in another two patients. Two of the six patients had paroxysmal kinesigenic dyskinesias and the remaining four patients had paroxysmal nonkinesigenic dyskinesias. Choreoathetosis (n = 3), myoclonus (n = 2), postural tremor (n = 5), and dysarthria (n = 3) were observed. Benzodiazepines appeared beneficial in three of six patients. Two patients with HIV-associated dementia and paroxysmal nonkinesigenic dyskinesia had a progressive course to death. Autopsy of a patient with paroxysmal nonkinesigenic dyskinesias revealed intense astrogliosis and loss of calbindin-positive neurons in the subcortical gray matter. CONCLUSIONS: Paroxysmal dyskinesias may present as a primary HIV-1-induced neurologic syndrome. The occurrence of paroxysmal dyskinesias is associated with neuronal injury and loss in the subcortical gray matter but the mechanism remains unknown.

AIDS Dementia Complex↗

PubMed1999

Effects of theophylline on plasma levels of interleukin-4, cyclic nucleotides and pulmonary functions in patients with chronic obstructive pulmonary disease.

In order to measure the plasma levels of interleukin-4 (IL-4), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in patients with chronic obstructive pulmonary disease (COPD) and observe the effects of oral theophylline on them, we divided 28 COPD patients into COPD experimental group and COPD control group. Plasma levels of IL-4, cAMP and cGMP as well as parameters of pulmonary function tests were measured in these 2 groups before and after 2 weeks of treatment with oral theophylline (Protheo, 400 mg, qd) or placebo. Plasma levels of IL-4 and cGMP were significantly elevated in patients with COPD as compared with normal controls (P < 0.05), while cAMP and cAMP/cGMP were significantly lower than those in controls (P < 0.01). Plasma level of IL-4 was inversely correlated with forced expiratory volume at the first second (FEV1) and with maximum expiratory flow rate at 50% of forced vital capacity (V50) (both r = -0.46, P < 0.05) while it was directly correlated with the scores of the clinical manifestations (r = 0.57, P < 0.05) in COPD patients. Two weeks after treatment with theophylline, IL-4 and cGMP in COPD experimental group were decreased significantly while cAMP and cAMP/cGMP increased significantly (P < 0.05). The change of IL-4 was inversely correlated with the changes of FEV1 and V50 (r = -0.53 and -0.54, respectively, P < 0.05). Two weeks after placebo treatment, the COPD control group did not show such changes. We are led to conclude that IL-4 might play a role in the pathogenesis of the airway inflammation and air flow limitation in COPD patients and the mechanisms of theophylline's therapeutic effects of attenuating air-flow limitation may partially depend on its anti-inflammatory effects on the airways which, in turn, is dependent on its inhibitory effects on some inflammatory mediators such as IL-4.

Aged↗

PubMed1999

Ethanol-extracted soy protein isolate results in elevation of serum cholesterol in exogenously hypercholesterolemic rats.

Soy protein preparations were reported to have hypocholesterolemic actions in experimental animals and humans, while the active components and the mechanism by which this occurs are not clarified yet. The objective of this study is to address these issues by using exogenously hypercholesterolemic rats which are susceptible to dietary cholesterol. Two groups of five rats (male, 12-wk-old) were fed on AIN 93G-based diet with soy protein isolate (SPI) or ethanol-extracted SPI (EE-SPI) for 2 wk. EE-SPI was prepared by ethanol extraction to remove isoflavones and other components. Concentrations of serum and liver total cholesterol were lower in rats fed SPI than in those fed EE-SPI. The abundances of mRNA for 7alpha-hydroxylase and low density lipoprotein receptor in the liver were lower in EE-SPI group than those in SPI group. These results suggest that the ethanol extract from SPI has a factor(s) to alleviate hypercholesterolemia by increasing the removal of cholesterol from serum through the receptor pathway and then from liver through enhancement of bile acid synthesis.

Animals↗

PubMed1999

Antisense oligodeoxynucleotides targeting internal exon sequences efficiently regulate TNF-alpha expression.

ABSTRACT Exon sequences upstream of splice sites play a critical role in mRNA processing, which is dependent on spliceosome interactions with these sites. Using antisense oligodeoxynucleotides (ODN), we targeted these and other sequences of the proinflammatory tumor necrosis factor-alpha (TNF-alpha) gene because it is multiply spliced and has been difficult to regulate with ODN in the past. ODN targeting exon sequences upstream of the donor splice sites of internal exons 2 (ORF4) and 3 (ORF6) significantly reduced TNF-alpha levels in stimulated U937 cells by 62%+/-7% and 51%+/-9%, respectively, in a dose-dependent manner but did not affect interleukin-6 (IL-6) levels. In contrast, ODN targeting the exon sequences downstream of the acceptor splice sites of exons 1, 2, and 3 failed to reduce TNF-alpha levels significantly under the same conditions. End-phosphorothioated ORF4 (ORF4-PE) significantly reduced TNF-alpha mRNA levels by greater than 80% (p < 0.001) and protein levels by 60% (p < 0.001) in U937 cells. ORF4-PE reduced newly synthesized TNF-alpha protein levels by >80% in lipopolysaccharide (LPS)-stimulated human macrophages, by greater than 60% in phorbol myristate acetate/phyto-hemagglutinin (PMA/PHA)-stimulated human peripheral blood mononuclear cells (PBMC), and by approximately 50% in LPS-stimulated murine monocytes. These results suggest that exon sequences flanking donor splice sites are highly susceptible target domains for antisense inhibition of TNF-alpha gene expression.

Animals↗

PubMed1999

Concentration of serum lipids and aortic lesion size in female and male apo E-deficient mice fed docosahexaenoic acid.

Apolipoprotein (apo) E-deficient mice were fed an atherogenic diet with either 1% ethyl ester docosahexaenoic acid (DHA) or safflower oil (SO) as a source of linoleic acid for 8 week. Both genders fed DHA had higher proportions of eicosapentaenoic acid and DHA, and lower proportions of linoleic and arachidonic acids in the liver and serum phospholipids than those fed SO. Males fed DHA had greater liver weight and tended to have higher concentrations of serum lipids and liver cholesterol than those fed SO, and there were opposite trends in females. Dietary fats and gender led to no significant effect on lesion sizes in aortic arch and thoracic plus abdominal aorta. These results indicate that the interactive action of sex-related factor(s) with dietary polyunsaturated fatty acids is involved in metabolic changes of serum lipids in apoE-deficient mice, and addition of DHA, compared with addition of SO, is not effective to abolish the atherosclerosis in this animal model.

Animals↗

PubMed1999

[The increased reactivity of isolated pulmonary artery rings from rats with hypoxia-induced pulmonary hypertension to activator of protein kinase C].

OBJECTIVE: To observe the reactivity of isolated pulmonary artery rings from rats with chronic hypoxic pulmonary hypertension (HPH) to protein kinase.C (PKC) activator. METHODS: Pulmonary artery rings from adult rats exposed to normobaric hypoxia for two weeks and normal rats were isolated for measurement of isometric contractions to PMA, the specific activator of PKC. Responses were examined as follows: (1) The maximal response (P(1)) to 0.5 micromol/L PMA and the time required to achieve a half-maximal response to 0.5 micromol/L PMA (t(1/2)); (2) Dose-response curve in response to PMA (0.01 - 10.0 micromol/L) and the dose of PMA that produced a contractile response as 50% of the maximal response (P(0)) to 80 mmol/L KCl (EC(50) KCl). RESULTS: P(1) of hypoxic group (34.3 +/- 2.4) P(0)% was greater than that of normal group [(26.2 +/- 2.9) P(0)%, n = 6, P < 0.05)], t(1/2) and EC(50) KCl of hypoxic group [(27 +/- 7) min, and (0.7 +/- 0.1) micromol/L] were smaller than those of normal group [(32 +/- 5) min, n = 6, P < 0.05, and (6.0 +/- 0.2) micromol/L, n = 12, P < 0.05]. CONCLUSIONS: The reactivity of pulmonary artery rings from hypoxic rats to PMA was enhanced, which indicates that protein kinase C may have an important role in the development of HPH.

Animals↗