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Biomedical subjects

Z Ni

Publications and source records attributed to Z Ni.

At least 19 recordsLinked to original sources
PubMed2001

Analyses of micronuclei in exfoliated epithelial cells from individuals chronically exposed to arsenic via drinking water in inner Mongolia, China.

The groundwater in Bayingnormen (Ba Men), located in Central West Inner Mongolia, China, is naturally contaminated with arsenic at concentrations ranging from 50 microg/L to 1.8 mg/L. Various adverse health effects in this region, including cancer, have been linked to arsenic exposure via drinking water. A pilot study was undertaken to evaluate frequencies of micronuclei (MN), as measures of chromosomal alterations, in multiple exfoliated epithelial cell types from residents of Ba Men chronically exposed to arsenic via drinking water. Buccal mucosal cells, airway epithelial cells in sputum, and bladder urothelial cells were collected from 19 residents exposed to high levels of arsenic in drinking water (527.5 +/- 24 microg/l), and from 13 control residents exposed to relatively low levels of arsenic in drinking water (4.4 +/- microg/L). Analytical results from these individuals revealed that MN frequencies in the high-exposure group were significantly elevated to 3.4-fold over control levels for buccal and sputum cells, and to 2.7-fold over control for bladder cells (increases in MN frequency significant at p < .001 for buccal cells; p < .01 for sputum cells; p < .05 for bladder cells). When smokers were excluded from high-exposure and control groups the effects of arsenic were observed to be greater, although only in buccal and sputum cells; approximately 6-fold increases in MN frequency occurred in these tissues. The results indicate that residents of Ba Men chronically exposed to high levels of arsenic in drinking water reveal evidence of genotoxicity in multiple epithelial cell types; higher levels of induced MN were observed in buccal and sputum cells than in bladder cells.

Adult↗
PubMed2001

Intrasubthalamic injection of 6-hydroxydopamine induces changes in the firing rate and pattern of subthalamic nucleus neurons in the rat.

The subthalamic nucleus (STN) receives dopaminergic projections from the substantia nigra pars compacta (SNc). To investigate the role of direct and indirect dopaminergic influences on STN neurons, the spontaneous activity was studied in four groups of animals: normal rats, rats with intrasubthalamic or intranigral injection of 6-hydroxydopamine (6-OHDA), and sham STN injection rats by using extracellular recordings 4 weeks postsurgery. After intrasubthalamic injection of 6-OHDA, the mean firing rate significantly decreased (7.29 +/- 0.39 spikes/sec, P < 0.01 vs. 11.13 +/- 0.59 spikes/sec in normal or 11.26 +/- 0.57 spikes/sec in sham group), and the percentage of STN neurons discharging regularly decreased significantly (81%, P < 0.05 vs. 90% in normal group or P < 0.01 vs. 92% in sham group) and that of bursty cells increased (19%, P < 0.05 vs. 10%; in normal group or P < 0.01 vs. 8% in sham group). In the group of rats with SNc lesion, the firing rate of subthalamic neurons did not show a significant difference (11.61 +/- 0.81 spikes/sec) compared with normal group. However, the firing pattern was dramatically changed: 74% of cells exhibited bursty pattern and only 26% of cells discharged regularly or slightly irregularly. Immunohistochemical results showed that intrasubthalamic injection of 6-OHDA induced a marked degeneration of dopaminergic cells in the lateral part of the ipsilateral SNc, whereas 6-OHDA injection into the SNc induced a total in situ lesion of dopamine cells. These results suggest that the SNc exerts an excitatory influence on STN neurons and that the loss of this dopaminergic projection could, at least partially, account for the changes in the firing pattern of STN neurons in the 6-OHDA rat model of parkinsonism.

Action Potentials↗
PubMed2001

Effect of salt loading on nitric oxide synthase expression in normotensive rats.

Elevation of arterial blood pressure (BP) with high salt intake in Dahl salt-sensitive rats is associated and perhaps, in part, due to downregulation of renal and vascular production of nitric oxide (NO) and nitric oxide synthase (NOS) expressions. Several recent studies have revealed a significant increase in BP in Sprague-Dawley rats on high salt intake. Given the apparent salt sensitivity of Sprague-Dawley rats, we hypothesized that chronic high salt intake may affect NO system in these rats in a manner resembling that reported in salt-sensitive (not salt-resistant) Dahl rats. The effects of a high salt diet (chow containing 8% NaCl) of 48-h or 3-week duration was studied on immunodetectable endothelial (eNOS), inducible (iNOS), and neuronal (nNOS) NOS expressions of relevant organs in male Sprague-Dawley rats. The results were compared with those obtained in the control animals fed a regular no-added salt diet (0.2% NaCl). Consumption of a high salt diet for 3 weeks induced hypertension (HTN) (158 +/- 6 v 115 +/- 5 mm Hg, P < .01) and widespread downregulation of iNOS expression in renal cortex, renal medulla, aorta, and heart. Similarly, chronic salt loading resulted in marked downregulation of eNOS expression in renal cortex and aorta and lowered expressions of nNOS in the brain, renal cortex, and renal medulla. In comparison, short-term salt loading resulted in significant reduction of iNOS in the renal cortex and aorta and of eNOS in the aorta together with significant elevation of nNOS expression in renal medulla and brain. Thus, chronic consumption of a high salt diet resulted in moderate HTN in normotensive Sprague-Dawley rats. This was accompanied by widespread downregulation of various NOS isotypes that undoubtedly contributed to the development and maintenance of HTN in this model.

Animals↗
PubMed2001

Effect of microiontophoretic application of dopamine on subthalamic nucleus neuronal activity in normal rats and in rats with unilateral lesion of the nigrostriatal pathway.

The subthalamic nucleus (STN) receives dopamine inputs from the substantia nigra but their implication in the pathophysiology of parkinsonism is still debated. Extracellular microrecordings were used to study the effect of microiontophoretic injection of dopamine and the D1 receptor agonist SKF 38393 on the activity of STN neurons in normal and 6-hydroxydopamine-lesioned rats under urethane anaesthesia. Dopamine and SKF induced an increase in the firing rate of the majority of STN neurons in both normal and 6-OHDA rats. In rats with 6-OHDA lesions, the percentage of firing rate increase did not differ from that of controls. When GABA, glutamate and dopamine were all applied to the same individual STN neurons, GABA induced an inhibitory effect and glutamate and dopamine caused an excitatory effect in both groups. This excitatory response was suppressed by the application of GABA. Systemic administration of apomorphine provoked a decrease in the firing rate of STN neurons in rats with 6-OHDA lesions. These results show that dopamine exerts an excitatory influence on STN neurons, suggesting that the inhibitory effect induced by the systemic injection of apomorphine is due to the GABAergic inputs from the globus pallidus as predicted by the current model of basal ganglia organization. In addition, we show that dopamine, GABA and glutamate can act on the same STN neuron and that GABA can reverse the excitatory effect of dopamine and glutamate, suggesting the predominant influence of GABAergic inputs to the subthalamic nucleus.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2001

Effect of severe aortic banding above the renal arteries on nitric oxide synthase isotype expression.

BACKGROUND: Severe aortic stenosis above the renal arteries leads to a reduction in renal perfusion, increased renin secretion, and elevation of arterial blood pressure above the stenotic site. Nitric oxide (NO) plays an important role in regulation of renal and systemic vascular resistance, renal blood flow, and Na(+) handling. Abdominal aortic banding provides an excellent model for simultaneous testing of the effects of increased and decreased pressure, flow, and shear stress in the same animal. METHODS: We studied protein expressions of endothelial NO synthase (eNOS), inducible NOS (iNOS), and neuroneal NOS (nNOS) isotypes in the renal cortex, renal medulla, heart, brain, and aorta segments above and below the stenosis site three weeks after abdominal aortic banding above the renal arteries. The results were compared with those obtained in the sham-operated controls. NOS isotype proteins were measured by Western blot. RESULTS: Compared with the control group, the banded group showed significant up-regulations of eNOS, iNOS, and nNOS in renal cortex and medulla. Likewise, heart eNOS, brain nNOS, and thoracic aorta eNOS proteins were significantly increased in the banded group. However, eNOS and iNOS expressions were unchanged in the aorta segment below the stenotic site. Likewise, iNOS expression in the heart and thoracic aorta remained unchanged in the banded animals. No significant difference was found in creatinine clearance or urinary protein excretion between the two groups. CONCLUSIONS: These findings clearly demonstrate the up-regulatory action of increased pressure on eNOS expression in the thoracic aorta and heart and of nNOS expression in the brain. These data further show up-regulation of all NOS isotypes in the kidney, which must have helped to mitigate the associated hypoperfusion.

Animals↗
PubMed2001

Enhanced nitric oxide inactivation in aortic coarctation-induced hypertension.

BACKGROUND: Abdominal aortic coarctation above the renal arteries leads to severe hypertension (HTN) above the stenotic site. We have recently shown marked up-regulations of endothelial nitric oxide synthase (eNOS) in heart and thoracic aorta and of neuronal NOS (nNOS) in the brain of rats with severe aortic coarctation above the renal arteries. We hypothesize that the presence of severe regional HTN in the face of marked up-regulation of NO system may be partly due to enhanced NO inactivation by reactive oxygen species (ROS) leading to functional NO deficiency. METHODS: Tissue nitrotyrosine (which is the footprint of NO interaction with ROS) was determined by Western blot in sham-operated control and aortic-banded (above renal arteries) rats three weeks postoperatively. Intra-arterial pressure and tissue nitrotyrosine (Western blot) were measured. RESULTS: The banded group showed a marked rise in arterial pressure measured directly through a carotid cannula (203 +/- 9 vs. 131 +/- 2 mm Hg, P < 0.01). Compared with the sham-operated controls, the banded animals exhibited significant increases in nitrotyrosine abundance in the heart, brain, and the aorta segment above the stricture. In contrast, nitrotyrosine abundance was unchanged in the abdominal aorta segment below the stricture wherein blood pressure was not elevated. CONCLUSION: Coarctation-induced HTN is associated with increased nitrotyrosine abundance in all tissues exposed to high arterial pressure, denoting enhanced ROS-mediated inactivation and sequestration of NO in these sites. This can, in part, account for severe regional HTN in this model. The normality of nitrotyrosine abundance in the abdominal aorta wherein blood pressure is not elevated points to the role of baromechanical factors as opposed to circulating humoral factors that were necessarily similar in both segments.

Animals↗
PubMed2001

Compensatory up-regulation of nitric-oxide synthase isoforms in lead-induced hypertension; reversal by a superoxide dismutase-mimetic drug.

Chronic exposure to low levels of lead causes hypertension (HTN) that is, in part, due to increased inactivation of nitric oxide (NO) by reactive oxygen species (ROS). The latter results in functional NO deficiency and compensatory up-regulation of NO synthase (NOS). We have previously shown evidence for increased hydroxyl radical (*OH) activity in rats with lead-induced HTN. Since in the biological systems *OH is primarily derived from superoxide (O2*) we hypothesize that lead-induced oxidative stress and HTN must be due to increased O2* production and as such could be ameliorated by administration of a cell-permeable O2* scavenger. We, therefore, studied the effects of the superoxide dismutase (SOD)-mimetic drug tempol (15 mmol/kg/day i.p. x 2 weeks) and placebo in lead-exposed (given lead acetate, 100 ppm in the drinking water for 12 weeks) and normal control rats. Lead exposure resulted in a marked elevation of blood pressure, a significant reduction in urinary NO metabolites (NO(chi)) excretion, and up-regulations of endothelial and inducible NOS abundance in the kidney, aorta, and heart and of neuronal NOS in the cerebral cortex and brain stem. Administration of tempol ameliorated HTN, increased urinary NO(chi) excretion, and reversed the compensatory up-regulation of NOS isoforms in rats with lead-induced HTN. These abnormalities recurred within 2 wk after discontinuation of tempol. In contrast to the lead-exposed rats, the normal control rats showed no change in either blood pressure, urinary NO(chi) excretion, or tissue NOS expression in response to either administration or discontinuation of tempol. Thus, the study supports the presence of increased O2* activity and its role in the pathogenesis of HTN and altered NO metabolism in lead-exposed animals.

Animals↗
PubMed2000

Analysis of K-ras and p53 mutations in mesotheliomas from humans and rats exposed to asbestos.

Malignant mesothelioma is known to be associated with asbestos exposure. However, the mechanism of mesothelial carcinogenesis in relation to the activation of proto-oncogenes or inactivation of tumor suppressor genes remains unclear. In this study, the PCR-Primer Introduced Restriction Site (PCR-PIRS) assay was employed to examine mutations in the K-ras proto-oncogene in mesothelioma tissues from workers exposed to asbestos and from rats treated with asbestos. Mutations in exons 5-8 of the p53 tumor suppressor gene were determined by direct DNA sequence analysis. Results of the PCR-PIRS analysis revealed no mutations in codons 12, 13 or 61 of the K-ras gene in any of the 17 human or 22 rat mesothelioma tissue samples. These results were confirmed by direct DNA sequence analysis. No mutations were found in exons 5-8 of the p53 gene in any of the mesothelioma tissue samples analyzed. These results and the results reported by others indicate that the K-ras proto-oncogene and p53 tumor suppressor gene may not play a critical role in the induction of mesothelioma by asbestos either in humans or in rats.

Animals↗
PubMed2000

High frequency stimulation of the STN influences the activity of dopamine neurons in the rat.

The effect of high frequency stimulation (HFS) of the subthalamic nucleus (STN) on the spontaneous activity of substantia nigra pars compacta (SNc) dopaminergic neurons was investigated in normal rats and in rats with globus pallidus (GP) lesions. In normal rats, the spontaneous activity of SNc neurons did not significantly differ from that of rats with GP lesions (4.2+/-2.2 versus 4.4+/-2.6 spikes/s). STN-HFS induced an increase of firing rate in the majority of tested cells in normal (76%) and GP-lesioned rats (73%) with an after-effect of 34.4+/-3.4 and 33.2+/-3.1 s, respectively. These results demonstrate that STN-HFS influences the activity of the SNc dopaminergic neurons by increasing their firing rate and that this increase of activity is independent of the globus pallidus.

Action Potentials↗
PubMed2000

Inhibition of constitutively activated Stat3 signaling pathway suppresses growth of prostate cancer cells.

Overexpression of interleukin 6, a downstream target of the GBX2 homeobox gene, has been linked to the progression of prostate cancer. The Janus kinase-signal transducers and activators of transcription signaling pathway transmits interleukin 6-mediated signals from cell surface receptors to the target genes in the nucleus and is critical in mediating cellular growth and differentiation. We demonstrate that cells derived from both rat and human prostate cancers have constitutively activated Stat3, with Stat3 activation being correlated with malignant potential. Blockade of activated Stat3 by ectopic expression of a dominant-negative Stat3 in human prostate cancer cells significantly suppresses their growth in vitro and their tumorigenicity in vivo. Furthermore, the Janus kinase inhibitor, tyrphostin AG490, inhibited the constitutive activation of Stat3 and suppressed the growth of human prostate cancer cells. These results indicate that activation of Stat3 signaling is essential in the progression of prostate cancer cells and suggest that targeting Stat3 signaling may yield a potential therapeutic intervention for prostate cancer.

Animals↗
PubMed2000

Interleukin-6 induces prostate cancer cell growth accompanied by activation of stat3 signaling pathway .

BACKGROUND: Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates growth and differentiation of various types of malignant tumors, including prostate carcinomas. The levels of IL-6 are elevated in sera of patients with metastatic prostate cancer. In this study, we evaluate the role of IL-6 in the growth regulation of prostate cancer cells. METHODS: Expression of IL-6 and its receptors in human prostate cancer cells was measured by ELISA and RT-PCR. The effects of IL-6 on cell growth were evaluated by ectopically expressing IL-6 cDNA into IL-6-negative LNCaP human prostate cancer cells. Stat3 DNA binding activities were analyzed by electromobility shift assay and supershift assay. RESULTS: Expression of IL-6 was detected in the androgen-insensitive prostate cancer cell lines (i.e. , TSU, PC3, and DU145), but not in the androgen-sensitive LNCaP cell line. IL-6 receptors, including both IL-6-specific receptor alpha chain and gp130 signal transducer, are expressed in all human prostate cancer cell lines (i.e., LNCaP, TSU, PC3, and DU145). Overexpression of IL-6 by ectopically expressing IL-6 into IL-6-negative LNCaP human prostate cancer cells significantly increased clonogenic ability and cell proliferation in vitro compared to the IL-6-negative parental LNCaP cells and the antisense controls. This growth stimulation by IL-6 was accompanied by activation of the Stat3 signaling transduction pathway. CONCLUSIONS: IL-6 is an autocrine growth factor for LNCaP human prostate cancer cells; the effects of IL-6 on prostate cancer cell growth are mediated through the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway.

Antigens, CD↗
PubMed2000

Identification of a hybrid-specific expressed gene encoding novel RNA-binding protein in wheat seedling leaves using differential display of mRNA.

A hybrid-specific expressed cDNA fragment, designated as AG5, has been identified in wheat seedling leaves using differential mRNA display. AG5 contains an open reading frame (ORF) encoding 183 amino acid residues. Comparison with amino acid sequences in GenBank revealed that the AG5 protein is homologous to a group of Gly-rich proteins with consensus sequence-type RNA-binding domains (CS-RBD). Structural analysis showed that AG5 protein contains five motifs, including a consensus sequence-type RNA-binding domain near its N-terminus, arginine/aspartic acid repeats and a Gly-rich region in its center, a Cys-X2-Cys-X4-His-X4-Cys (CCHC) zinc finger motif in the Gly-rich region, and TrySer2ArgAsp2Arg repeats towards its C-terminus. Of all previously described RNA-binding proteins, only RZ-1 from tobacco has a similar structure to the AG5 protein, but RZ-1 lacks a TrySer2ArgAsp2Arg repeat motif, indicating that the two proteins may belong to a family of closely related proteins in plants. The possible role of AG5 and its relation to wheat heterosis are discussed.

Amino Acid Sequence↗
PubMed2000

Down-regulation of renal endothelial nitric oxide synthase expression in experimental glomerular thrombotic microangiopathy.

Infection with certain strains of Escherichia coli and endotoxemia results in renal glomerular thrombotic microangiopathy (TMA) characterized by endothelial swelling and prominent glomerular microthrombus formation. Nitric oxide (NO) is an endogenous biologic modulator with diverse physiologic functions including vasodilation and inhibition of platelet adhesion and aggregation. NO is synthesized from conversion of L-arginine to L-citrulline by a family of NO synthases (NOS), which include constitutive and inducible isoforms. Indirect evidence supports the hypothesis that TMA is associated with depressed intrarenal NO production. However, the effect of TMA on renal tissue NOS expression has not been fully elucidated. We studied rats with TMA induced by iv bolus injection of high dose (20 mg/kg) E. coli endotoxin. Subgroups of six animals each were sacrificed before or at 30, 90, 180, 360, and 720 minutes after the administration of endotoxin. Renal histology and tissue expression of endothelial and inducible nitric oxide synthases (eNOS and iNOS) were examined. Additionally, we examined the effect of endotoxin on glomerular NO production, and eNOS and iNOS protein expression in vitro. Glomerular capillary thrombosis developed by 180 minutes after endotoxin administration in approximately half of the animals. The glomeruli without thrombotic lesions apparent by light microscopy disclosed early signs of TMA characterized by endothelial swelling, platelet accumulation/adhesion, and patchy fibrinogen deposition. These morphologic changes were associated with a marked reduction of renal tissue eNOS expression beyond 180 minutes after the endotoxin administration. The fall in eNOS expression was coupled with a significant rise in iNOS protein abundance, which was expressed largely by glomerular circulating neutrophils and endothelial cells, peritubular vascular endothelium, and collecting ducts of cortex and medulla. In vitro incubation of isolated glomeruli with endotoxin also resulted in a marked reduction in eNOS expression and a significant rise in iNOS content. Administration of E. coli endotoxin leads to a sustained fall in renal eNOS expression both in vivo and in vitro. The associated decline in intrarenal endothelial NO production/availability may result in renal vasoconstriction and a hypercoagulative state, which may contribute to the pathogenesis of endotoxin-induced TMA.

Animals↗
PubMed2000

Effect of antioxidant therapy on blood pressure and NO synthase expression in hypertensive rats.

Earlier studies have demonstrated evidence for increased reactive oxygen species, enhanced NO synthase (NOS) expression, and elevated NO production in spontaneously hypertensive rats (SHR). Given the negative-feedback regulation of NOS by NO, we hypothesized that enhanced NO inactivation by ROS may contribute to compensatory upregulation of NOS in SHR. The present study was designed to test this hypothesis. Eight-week-old male SHR and Wistar-Kyoto rats were treated for 3 weeks with either a placebo or the potent antioxidant, lazaroid (desmethyltirilazad, 10 mg. kg(-1). d(-1), by gastric gavage). Tail arterial blood pressure, urinary excretion of NO metabolites (ie, nitrate and nitrite), and immunodetectable NOS isotype proteins in the vascular, renal, cardiac, and cerebral tissues were measured. The placebo-treated SHR group showed a marked elevation of blood pressure and a significant upregulation of aorta, kidney, and cardiac tissue endothelial and inducible NOS (eNOS and iNOS, respectively) proteins and of brain and renal tissue neuronal NOS. Lazaroid therapy ameliorated hypertension and mitigated the upregulation of eNOS and iNOS in vascular, renal, and cardiac tissues but had limited effect on the expression of renal and brain neuronal NOS. In contrast, lazaroid therapy had no effect on blood pressure, urinary nitrate and nitrite excretion, or tissue NOS isotype expressions in the Wistar-Kyoto group. These findings support the role of oxidative stress in the genesis and/or maintenance of hypertension and compensatory upregulation of the expression of eNOS and iNOS in SHR.

Animals↗
PubMed2000

Changes in the firing pattern of globus pallidus neurons after the degeneration of nigrostriatal pathway are mediated by the subthalamic nucleus in the rat.

Changes in the neuronal activity of globus pallidus (GP) have been shown in animal models of parkinsonism. In order to study the implication of the subthalamic nucleus (STN) in these changes, the effects of STN lesions alone or in combination with 6-hydroxydopamine (6-OHDA) -induced damage to the substantia nigra compacta (SNc) were examined in rats using electrophysiological recordings of GP cells. In normal rats, the firing rate was 22.1+/-1.4 spikes/s. The pattern was regular in 45%, irregular in 49% and bursty in 6% of the cases. In rats with STN lesions, the firing rate of GP units (20.15+/-1.25 spikes/s) did not differ from that of normal rats and only regular (46%) and irregular (54%) cells were found; a bursty pattern was not observed. 6-OHDA lesions of the SNc induced no change in the firing rate of GP neurons (21.5+/-1.4 spikes/s, P>0.05) but a significant decrease in the percentage of regular cells (27%, P<0.001), a significant increase in burst cells (21%, P<0.001) with no change in the percentage of irregular units (52%) were observed. In rats with combined SNc and STN lesions, the firing pattern did not change from that of normal rats. The present results show that STN lesions induced the disappearance of bursts in normal rats and normalization of firing pattern in the GP units of rats with 6-OHDA lesions suggesting that the STN plays an important role in the modulation of the pattern of activity of GP neurons which may account for the therapeutic effect of STN lesions in Parkinson's disease.

Animals↗
PubMed2000

[The prevention of primary liver cancer by selenium in high risk populations].

OBJECTIVE: To study the preventive effects of selenium on primary liver cancer. METHODS: After screening of blood samples in 18,000 males from 20 to 65 years-old in Qidong, Jiangsu province (a high risk area for liver cancer), 2,065 cases of HBsAg positive, AFP negative and normal liver function (normal ALT values) were found. The subjects were randomly divided into two groups, based on their residence areas; 1,112 subjects (experimental group) received one tablet of sodium selenite (0.5 mg Se) every day and 953 subjects (control group) received one placebo tablet every day. RESULTS: During three years of intervention and follow up, the blood selenium concentration and glutathione peroxidase activity of the subjects in the experimental group were increased and had significant difference as compared with those of the control group (P < 0.01). At the same time, the prevalence rate of micronucleus cells in peripheral blood lymphocytes in the experimental group was significantly lower than that of the control group (P < 0.01), and the incidence of new liver cancer in the experimental group (3 057.55/10(6), 34 cases out of 1,112 subjects) was significantly lower than the control group (5 981.11/10(6); 57 cases out of 953 subjects) (P < 0.01). CONCLUSION: The results confirms that selenium supplementation in general populations lived in high risk is effective in the prevention of liver cancer and the using of selenium tablets is simple and feasible.

Adult↗
PubMed1999

Nitric oxide synthase isotype expression in salt-sensitive and salt-resistant Dahl rats.

Previous studies have suggested that salt-sensitive hypertension in humans and experimental animals may in part be due to dysregulation of the L-arginine/nitric oxide system. This study was conducted to determine the endothelial, inducible, and neuronal nitric oxide synthase expressions in the kidney, heart, aorta, and brain of salt-sensitive and salt-resistant Dahl rats. We studied salt-sensitive and salt-resistant Dahl rats maintained on high- (8%) and regular- (0.2%) salt diets for 3 weeks. Blood pressure was modestly elevated in both Dahl salt-sensitive and salt-resistant rats consuming regular diet and severely increased in sensitive but not resistant rats consuming the high-salt diet. The Dahl salt-sensitive animals showed a significant reduction in kidney, heart, and aorta inducible nitric oxide synthase protein abundance on the regular diet, with further reductions on the high-salt diet. In addition, the high-salt diet markedly downregulated endothelial nitric oxide synthase expression in the kidney and aorta but not in the heart of the Dahl salt-sensitive animals. The rise in blood pressure in the Dahl salt-sensitive rats on the high-salt diet was accompanied by a significant elevation of brain neuronal nitric oxide synthase protein. In contrast, salt-resistant animals showed no change in heart, kidney, and aorta endothelial or brain neuronal nitric oxide synthase and considerably less intense changes in inducible isotype than that seen in the salt-sensitive group in response to the high-salt diet. In conclusion, the study revealed a marked downregulation of inducible nitric oxide synthase in the Dahl salt-sensitive rats on the regular diet, with further reductions on the high-salt diet. Furthermore, Dahl salt-sensitive rats consuming the high-salt diet showed significant reductions of kidney and aorta endothelial nitric oxide synthase and an upregulation of brain neuronal nitric oxide synthase expression.

Analysis of Variance↗