Biomedical subjects

J T Cheng

Publications and source records attributed to J T Cheng.

At least 91 records · Page 5Linked to original sources

PubMed1998

Modification of superoxide dismutase (SOD) mRNA and activity by a transient hypoxic stress in cultured glial cells.

In order to understand the role of superoxide dismutase (SOD) in response to transient hypoxia or hypoxia-reperfusion in astrocytes, the present study performed an in vitro investigation using rat glial cells in culture. Hypoxia was induced by an incubation with nitrogen gas for 10 min and that followed a further reperfusion with air for 10 min was indicating as hypoxia-normoxia. Activity of SOD was determined by the reduction of nitroblue tetrazolium (NTB). Changes of mRNA for Cu,Zn-SOD or Mn-SOD were also characterized using Northern blotting analysis. Transient hypoxia increased the activity of Mn-SOD but not that of Cu,Zn-SOD in glial cells. Expression of mRNA for SOD was also elevated in cells received hypoxia and the mRNA level for Mn-SOD raised higher than that for Cu,Zn-SOD. In cells received hypoxia-reperfusion, these changes of SOD both the activity and the mRNA level were not observed. Otherwise, the SOD protein amount, both Cu,Zn-SOD and Mn-SOD, identified by Western blotting was not changed in glial cells receiving hypoxic stress or not. The obtained results suggest that gene expression and activity of Mn-SOD in glial cells can be activated in response to the transient hypoxic stress.

Animals↗

PubMed1998

Effects of nicotine on spontaneous and amphetamine-induced motor behaviors: the differences between nicotine tolerant and nontolerant rats.

This study was designed to investigate the effect of nicotine on spontaneous and amphetamine (AMP)-induced motor activity in rats with or without tolerance to nicotine. Tolerance were induced by treating the rats with nicotine (0.3 mg/kg, s.c.) 2 hr before receiving challenge doses. Motor activity including locomotion and stereotypy was monitored automatically by videocamera every 15 min for 90 min. The results indicated that: (1) Nicotine increased spontaneous locomotion at 0.15 or 0.3 mg/kg (s.c.) in naive rats and at 0.6 mg/kg in tolerant rats. Nicotine also slightly affected AMP-induced locomotion at 0.15, 0.3 or 0.6 mg/kg in both naive and tolerant rats, and (2) Nicotine increased spontaneous stereotypy at 0.3 or 0.6 mg/kg in naive rats only and showed no effect on AMP-induced stereotypy in either naive or tolerant rats. Comparing the results of spontaneous motor activity between naive and tolerant rats, it revealed behavioral desensitization in locomotion at low doses (0.15 or 0.3 mg/kg) and hyperlocomotion at higher dose (0.6 mg/kg), and revealed desensitization in stereotypy at 0.3 or 0.6 mg/kg. Moreover, nicotine had temporary (at 0-15 min interval) attenuating effect on AMP-induced locomotion in naive rats but showed a potentiating effect on AMP-induced locomotion in tolerant rats. The present results indicated that acute tolerance modified the action of nicotine in both spontaneous and AMP-induced locomotion, while stereotypy was changed only in the spontaneous one but not in the AMP-induced one. In other words, acute tolerance modified the effect of nicotine on locomotion-related dopaminergic system, and it affected the stereotypy-related dopaminergic system only in the spontaneous one but not in the AMP-induced one.

Adenosine Monophosphate↗

PubMed1998

Stimulatory effect of paeoniflorin on adenosine A-1 receptors to increase the translocation of protein kinase C (PKC) and glucose transporter (GLUT 4) in isolated rat white adipocytes.

In an attempt to understand the subcellular signals after activation of adenosine A-1 receptors, paeoniflorin was employed to incubate with rat white adipocytes in vitro. Translocation of protein kinase C (PKC) beta-subtype from cytosol to membrane was enhanced by an incubation with paeoniflorin in a concentration-dependent manner similar to that of porcine insulin. Also, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) inhibited this action of paeoniflorin in a concentration-related fashion and it markedly attenuated the action of paeoniflorin at a concentrations sufficient to block the action of adenosine. Moreover, chelerythrine inhibited the paeoniflorin-stimulated translocation of PKC in a way similar to that stimulated by porcine insulin. Subcellular inhibition is considered because stimulation of porcine insulin was not modified by DPCPX at concentrations sufficient to block adenosine A-1 receptors. Similar results were also observed in adipocytes regarding the translocation of glucose transporter (GLUT4) from cytosol to membrane. Thus, we found that paeoniflorin can activate adenosine A-1 receptors to increase the translocations of PKC and GLUT4, two major signals for glucose uptake, from cytosol to membrane of the white adipocytes in rats.

Adipocytes↗

PubMed1998

Inhibition of immune cell proliferation with haloperidol and relationship of tyrosine hydroxylase expression to immune cell growth.

Previous studies indicated that exogenous dopamine and its agonists directly regulated mitogen-induced immune cell proliferation. In this study, we further investigated role of endogenous dopamine in immune cell growth. Haloperidol, a general antagonist for dopamine receptors, could reduce the cell growth rate of T cell hybridoma (10I) and rat nervous pheochromocytoma cells (PC12). Tyrosine hydroxylase (TH) catalyzes the initial rate-limiting step of catecholamine biosynthesis in the nervous system. Flow cytometric analysis indicated the expression of TH in various immune cells. The presence of TH in PC12 cells was used as a control. Temporal studies indicated that the expression of TH increased during 10I cell growth. Both alpha-methyl-p-tyrosine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine reduced TH expression and cell growth in a dose-dependent manner. These results suggest that immune T cells express TH which is correlated to cell growth, and that dopamine released from these cells may bind to the receptors to act in an autocrine or paracrine way.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1998

An ex vivo evaluation of regulatory role of biogenic amines in rat seminal vesicle after pharmacological manipulation.

We studied the neural regulation of seminal vesicles (SV) by determining the changes of intraluminal pressure of rat SV in response to an electric stimulation of the lesser splanchnic nerve (LSN). After pharmacological manipulation with neurotoxin, the contents of monoamines and their metabolites in SV were estimated. In rats receiving electric stimulation of the LSN, an increase of intraluminal pressure was obtained with a reduction of the serotonergic turnover rate in SV. An intraperitoneal injection of DSP-4 (100 mg/kg), the noradrenergic neurotoxin, into rats decreased the level of norepinephrine (NE) in SV significantly but did not influence this functional response. Also, the intraluminal pressure was lowered by an intrathecal injection of 6-OHDA (20 microg/rat) to denervate spinal monoaminergic nerves in rats although the contents of monoamines in SV were not changed. This indicates that noradrenergic neurotransmission appears unimportant in this regulation. The lowering of intraluminal pressure in rats by 6-OHDA is mainly related to an attenuation of dopaminergic neuroregulation from the decrease of turnover rate of DA. Otherwise, an intrathecal injection of 5,7-DHT (60 microg/rat) to abolish spinal serotonergic nerves did not influence the level of monoamines in SV but increased the intraluminal pressure indicating an involvement of inhibitory regulation from spinal serotonergic pathway. These results suggest that contraction by electric stimulation of the LSN in Wistar rat SV is mainly regulated by the dopaminergic nervous pathway and an inhibitory regulation of the serotonergic nervous pathway from spinal cord while the noradrenergic nervous system seems unimportant for this regulation.

5,7-Dihydroxytryptamine↗

PubMed1998

The effect of stevioside on blood pressure and plasma catecholamines in spontaneously hypertensive rats.

Stevioside is a sweet-tasting glycoside, composed of stevia, a diterpenic carboxylic alcohol with three glucose molecules, mainly used as a substitute for non-alcoholic sweetener. It has previously been shown to reduce blood pressure in studies in animals and human. The effect of intravenous stevioside on the blood pressure was studied in spontaneously hypertensive rats (SHR). The hypotensive effect on both systolic and diastolic blood pressure was dose-dependent for intravenous doses of 50, 100 and 200 mg/kg in conscious SHR. The maximum reductions in systolic and diastolic blood pressure were 31.4 +/- 4.2% and 40.8 +/- 5.6% (mean +/- SEM) respectively and the hypotensive effect lasted for more than 60 min with a dose of 200 mg/kg. Serum dopamine, norepinephrine and epinephrine levels were not changed significantly 60 min after intravenous injection of stevioside 100 mg/kg in anesthetized SHR. The present data show that stevioside given intravenously to conscious SHR was effective in blood pressure reduction and there was no change in serum catecholamines in anaesthetized animals with this natural compound.

Animals↗

PubMed1998

Stimulatory effect of octopamine on beta 3-adrenoceptors to lower the uptake of [14C]-deoxy-D-glucose into rat adipocytes in vitro.

1. The effect of octopamine on beta 3-adrenoceptors has been studied in isolated adipocytes of Wistar rats using uptake of [14C]-deoxy-D-glucose as the indicator. 2. Octopamine (0.1-1 nmol 1-1) induced a concentration-dependent decrease of [14C]-deoxy-D-glucose uptake into the adipocytes and this inhibition was not influenced by haloperidol at concentrations sufficient to block dopaminergic receptors. 3. Pindolol and propranolol reversed this inhibition of octopamine in a concentration-dependent manner. The effect of octopamine was reduced in the presence of Rp-cyclic AMPS triethylamine, the membrane-permeable antagonist of cyclic AMP (cAMP), indicating the mediation of cAMP in this inhibition. 4. A direct effect of octopamine on beta 3-adrenoceptors was proved using the application of antibodies. In the presence of an antibody for beta 3-adrenoceptors, the actions of octopamine were concentration-dependently reduced in a manner similar to the decrease of BRL37344-induced inhibitions. 5. The same degree of diminished activities for octopamine as that of BRL37344, the well-known specific agonist of beta 3-adrenoceptors, was also obtained in isoprenline-desensitized adipocytes. Insulin-stimulated uptake of [14C]-deoxy-D-glucose into adipocytes was not modified by isoprenaline induced desensitization. 6. These results suggest that octopamine can activate beta 3-adrenoceptors to lower the glucose uptake through an increase of cAMP in rat white adipocytes.

Adipocytes↗

PubMed1998

In vivo evaluation of serotonergic agents and alpha-adrenergic blockers on premature ejaculation by inhibiting the seminal vesicle pressure response to electrical nerve stimulation.

OBJECTIVE: To evaluate the effect of drugs on premature ejaculation using a rat animal model in which the seminal vesicle was electrically stimulated via its lesser splanchnic nerve and changes in the pressure response monitored. MATERIALS AND METHODS: Male Wistar rats (aged 12-14 weeks) were injected intravenously with prazosin and serotonergic agents (serotonin, clomipramine, fluoxetine, imipramine and indatraline) at various concentrations 10 min before electrical nerve stimulation (ENS) of the lesser splanchnic nerve; the initial increase in seminal vesicle pressure in response to ENS was then compared. RESULTS: The pressure response to ENS was reduced in the presence of prazosin or serotonergic agents. The mean (SEM) maximum inhibition values were 84.1 (8.9%) by fluoxetine at 0.1 mg/kg, 67.9 (8.7)% by prazosin at 0.1 mg/kg, 60.9 (11.0)% by serotonin at 3 mg/kg, 54.9 (4.6)% by clomipramine at 3 mg/kg, 30.0 (11.0)% by imipramine at 0.1 mg/kg, and 20.9 (4.3)% by indatraline at 0.1 mg/kg. From the concentration-response curve, the potency of prazosin was lower than that of fluoxetine, but was higher than that of serotonin or clomipramine. CONCLUSIONS: Like serotonin, fluoxetine and clomipramine can reduce the pressure response of the seminal vesicle to ENS. Among these inhibitory agents, including prazosin, fluoxetine was the most effective and may be valuable for the clinical treatment of ejaculatory dysfunction in man.

Adrenergic Uptake Inhibitors↗

PubMed1998

Inhibition of protein kinase C translocation from cytosol to membrane by chelerythrine.

Protein kinase C (PKC) is regarded as an important signal in cellular responses. Chelerythrine, the alkaloid in Zanthoxylum simulans, was recently introduced as a specific blocker of PKC phosphorylation. The present study demonstrated an inhibitory effect of chelerythrine on the translocation of PKC from cytosol to membrane using Western blotting analysis. An increase of PKC translocation from cytosol to the membrane was observed in isolated ileal synaptosomes incubated with phorbol 12-myristate 13-acetate (PMA) to reach the plateau at 30 min later. Pretreatment with chelerythrine for 20 min attenuated this action of PMA in a concentration-dependent manner and the inhibition of PKC alpha translocation was similar to that of PKC beta. An inhibitory effect of chelerythrine on the translocation of PKC is considered in addition to the inhibition of PKC phosphorylation.

Alkaloids↗

PubMed1998

Gene transfer via pollen-tube pathway for anti-fusarium wilt in watermelon.

In order to obtain transgenic fusarium wilt resistant watermelon plants, squash DNA was introduced into the ovaries of watermelon plants via the pollen-tube pathway. The introduction of foreign genes into ovaries was accomplished using co-transformation with the CaMV35S-GUS as a marker. Transformed watermelon plants contained integrated copies of the GUS activity and the seeds of transformed progeny produced a blue color when stained with 5-bromo-4-chloro-3-indolyl glucuronide, whereas seeds from untransformed control plants did not. Of 200 transformed seedlings, ten were wilt resistant. The presence of the GUS activity in the genome of stable transgenic seedlings was confirmed by Southern blot analysis. Furthermore, the generation of random amplified polymorphic DNA (RAPD) fingerprints using primers with embedded restriction sites showed amplification products unique to these transgenic plants. Primers OPA-1 and OPA-9 gave distinct band patterns of genomic DNA using the polymerase chain reaction.

DNA, Plant↗

PubMed1998

Production and characterization of monoclonal antibodies against Tal1 oncoprotein.

TAL1 (or SCL) oncogene functions as a transcription regulatory factor that is necessary for the early development of all hematopoietic lineages. Aberrant expression of Tall protein in T cells is the cause of T-cell acute lymphoblastic leukemia (T-ALL) in children. We generated two hybridomas that secreted monoclonal antibodies (MAbs) that reacted strongly with GST-TAL(1-210) but not with GST fusion protein in ELISA assay. These two MAbs, TWN3 and TWN60, recognized TALI oncoprotein expressed in transfected COS-1 cells by Western blotting. In addition, both MAbs were also effective in detecting TAL1 oncoprotein in leukemic cells by immunoprecipitation and immunocytochemistry. Therefore, they should be useful in the studies of Tall protein functions in both hematopoietic development and oncogenesis.

Animals↗

PubMed1998

Renal denervation prevents and reverses hyperinsulinemia-induced hypertension in rats.

Experiments were performed to evaluate the role of the renal nerves in hyperinsulinemia-induced hypertension. Male Sprague-Dawley rats were made hyperinsulinemic by insulin infusion via osmotic minipumps implanted subcutaneously (3.0 mU/kg per minute for 6 weeks). Rats with vehicle infusion served as controls. Bilateral renal denervation was performed either at the beginning of or 4 weeks after insulin infusion. The systolic blood pressure was measured by the tail-cuff method twice a week. Food and water intake and urine flow were measured daily. The results showed that sustained insulin infusion significantly increased plasma insulin concentrations from 277.7+/-25.8 pmol/L to 609.9+/-22.2 and 696.7+/-23.0 pmol/L by the end of weeks 4 and 6, respectively (P<0.05). Systolic blood pressure was significantly increased from 135+/-3 to 157+/-3 and 159+/-2 mm Hg (P<0.05) at the corresponding time points. There was a significant increase in the plasma norepinephrine concentration after insulin infusion, whereas no significant changes in plasma triglyceride and glucose concentrations, water intake, urine flow, sodium excretion, sodium gain, and body weight gain were observed. Bilateral renal denervation depleted renal norepinephrine stores and prevented the development of hyperinsulinemia-induced hypertension. After hyperinsulinemia-induced hypertension had been fully established (from 134+/-2 to 157+/-2 mm Hg), bilateral renal denervation reversed the elevated systolic blood pressure to normotensive levels within 2 weeks. Transient denervated diuresis and natriuresis were observed. These results indicate that chronic hyperinsulinemia-induced hypertension requires the presence of intact renal nerves in rats.

Animals↗

PubMed1998

Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy.

The most common form of glomerular disease seen in association with hepatitis C virus (HCV) infection is membranoproliferative glomerulonephritis, with or without associated cryoglobulinemia. This study examines four cases of fibrillary glomerulonephritis and two cases of immunotactoid glomerulopathy in association with HCV infection. Findings at presentation included proteinuria, renal insufficiency, and hematuria. Renal biopsy revealed a membranoproliferative pattern of glomerular disease in five cases, and a membranous glomerulopathy with mesangial proliferative features in one. On immunofluorescence, all cases stained with IgG and C3. Electron microscopy revealed fibrils of the expected diameter, 16 to 28 nm in fibrillary glomerulonephritis and 33 to 45 nm in immunotactoid glomerulopathy. In only one case were cryoglobulins detected (at low titer and on only one of three assays). Antiviral therapy was not given in any of the six cases. Outcomes were mixed, with progression to renal failure occurring in two patients and persistent proteinuria with stable or improved renal function in three. Follow-up is not available on the sixth case. Both fibrillary glomerulonephritis and immunotactoid glomerulopathy have features that overlap with cryoglobulinemic glomerulonephritis. The relatedness of these three entities in a subset of patients with HCV infection suggests a common pathogenic mechanism of glomerular deposition of organized deposits.

Adult↗

PubMed1998

Serum endothelin and atrial natriuretic peptide in cirrhotic patients with ascites and hepatorenal syndrome.

BACKGROUND: The pathogenesis of cirrhotic ascites and hepatorenal syndrome remains unresolved. The involvement of both endothelin-1 and atrial natriuretic peptide have recently been suggested. This study investigated the concentrations of serum endothelin and atrial natriuretic peptide in cirrhotic patients. METHODS: Seven healthy subjects and 31 cirrhotic patients were studied. Cirrhotic patients were divided into three groups: Group I, 16 cirrhotic patients without ascites; Group II, 10 cirrhotic patients with ascites, but without hepatorenal syndrome; and Group III, five cirrhotic patients with hepatorenal syndrome and ascites. Their sera were analyzed for endothelin-1 and atrial natriuretic peptide concentrations. RESULTS: Cirrhotic patients with ascites, Group II and Group III, had higher plasma endothelin-1 concentrations (15.9 +/- 2.3 pg/ml and 24 +/- 2.1 pg/ml, respectively) than normal subjects and compensated cirrhotics (3.8 +/- 0.7 pg/ml and 6.4 +/- 1.1 pg/ml, respectively); p < 0.001). Atrial natriuretic peptide concentrations were also significantly higher in cirrhotic patients than in normal subjects (p < 0.025). Plasma endothelin-1 concentration had a negative correlation with creatinine clearance (r = -0.65, p < 0.001), as did atrial natriuretic peptide concentrations (r = -0.44, p = 0.012). Plasma endothelin-1 correlated significantly with atrial natriuretic peptide concentrations (r = 0.38, p = 0.035). CONCLUSIONS: Both endothelin-1 and atrial natriuretic peptide concentrations were elevated in cirrhotic patients with ascites and hepatorenal syndrome. Endothelin-1 may have a negative impact on renal function. Our data also suggested that impaired responsiveness rather than impaired secretion of atrial natriuretic peptide is responsible for sodium retention in cirrhotic patients with ascites.

Adult↗

PubMed1998

NitroG-L-arginine methyl ester decreases minimum alveolar concentration of isoflurane and reduces brain nitric oxide synthase activity in rats.

BACKGROUND: Nitric Oxide (NO), an endogenous messenger produced by the enzyme nitric oxide synthase (NOS), is recently introduced to be involved in inhalational anesthesia. We have previously reported that a specific NOS inhibitor, nitroG-L-arginine methyl ester (L-NAME), reduces the value of minimum alveolar concentration (MAC) for isoflurane anesthesia in rabbits. The purpose of this study is to evaluate the effects of the NOS inhibitor, L-NAME, on isoflurane MAC and NOS activity in rats. METHODS: Adult Wistar rats receiving isoflurane inhalation were randomly divided into two groups, with eight rats in each group. In the study group, L-NAME 30 mg/kg was given 60 min before the inhalation of isoflurane. Normal saline was given to the control group instead. The data of MAC, blood pressure (BP), and heart rate (HR) were recorded. The vital signs, such as EtCO2, PaO2, and temperature, were maintained within normal ranges. The activity of NOS in cerebellum was assessed by measuring the conversion of L-[3H] arginine to L-[3H] citrulline. All data were presented as mean +/- SD. Statistical analysis was performed using Student's t-test, where P < 0.05 was considered significant. RESULTS: In the presence of L-NAME (30 mg/kg), the MAC for isoflurane was markedly reduced from 1.6 +/- 0.20% (study group) to 1.0 +/- 0.09% (control group) (P < 0.05). The activity of cNOS in cerebellum was 220.09 +/- 23.64 (pmol/mg protein/30 min) in the control group, and in contrast a sharp reduction as low as to 115.40 +/- 24.85 (pmol/mg protein/30 min) was seen in the study group. CONCLUSIONS: The involvement of NO in the mechanism of isoflurane anesthesia can be demonstrated by the fact that the NOS inhibitor, L-NAME reduces the level of MAC and the cerebral NOS activity in rats.

Anesthetics, Inhalation↗

PubMed1997

Change of cardiac beta-adrenoceptors in lead-exposed rats.

The effect of lead on cardiac beta-adrenoceptors was studied. Wistar rats used in these trials were divided into seven groups of ten animals each (A-G). Of these, groups B was given drinking water containing 0.01% lead acetate, group C 0.05%, group D 0.1%, group E 0.5%, group F 1% and group G 2% for a period of 60 days. Group A was given pure water. A radioligand-binding assay fulfilling strict criteria of receptor affinity and density was used to quantify cardiac beta-adrenoceptors. Application of a trend test indicated that both blood and heart lead levels increased significantly from group A to group G (A < G), but that beta-adrenoceptor density decreased (G < A), whereas Kd did not vary among the seven groups. Linear regression analysis showed that decrease of cardiac beta-adrenergic receptor density was closely related to elevation of blood and heart lead levels. The results show that lead exposure results in a reduction of cardiac beta-adrenoceptor density.

Animals↗

PubMed1997

The role of free radicals in the release of noradrenaline from myenteric nerve terminals of guinea-pig ileum.

In an attempt to understand the role of free radicals in the regulation of sympathetic neurotransmission, the in vitro secretion of noradrenaline (NA) from synaptosomal preparations of guinea-pig ileum was investigated. Release of endogenous NA was quantified by an electrochemical detection (HPLC-ECD). In the presence of superoxide dismutase (SOD) and catalase at concentrations sufficient to scavenge the free radicals, secretion of NA was attenuated in samples with stimulation of 4-aminopyrine (4-AP) or not (spontaneous release). However, inducing superoxide radicals via the reaction of hypoxanthine with xanthine oxidase failed to modify the secretion of NA, both the 4-AP-stimulated release and the spontaneous secretion. Then, free radicals were induced in synaptosomes using hypoxia-normoxia exposure. Secretion of NA was markedly increased in samples receiving this treatment in a calcium-dependent way because it was attenuated by the removal of calcium chloride from bathing medium. An increase of SOD activity, both Mn-SOD and Cu, Zn-SOD, was also obtained by this exposure. Changes of SOD activities in response to free radicals produced by hypoxia-normoxia exposure in ileal synaptosomes can thus be considered. In conclusion, these results suggest that free radicals are formed to involve in the regulation of sympathetic neurotransmission via an increase of calcium influx to enhance the NA release in guinea-pig ileum.

Animals↗

PubMed1997

The role of nitric oxide in the control of plasma glucose concentration in spontaneously hypertensive rats.

Glucose homeostasis was studied in the spontaneously hypertensive rat (SHR). The fasting plasma glucose levels were similar in the SHR and normotensive Wistar-Kyoto (WKY) rat (102.7+/-2.4 vs. 107.4+/-4.2 mg/dl, P > 0.01). One hour after glucose challenge, the plasma glucose level was slightly but insignificantly increased in both SHR and WKY rat (117+/-2.5 vs. 114.3+/-3.2 mg/dl, P > 0.01). After N(G)nitro-L-arginine methyl ester (L-NAME) 20 mg/kg per day was administered intraperitoneally (i.p.) for 4 days, the plasma glucose level was significantly increased in the rats (SHR 167.3+/-4.9; WKY rat 136.0+/-4.8 mg/dl); the increase was significantly more pronounced in the SHR. The fasting insulin levels were similar in the SHR and WKY rats (2.3+/-0.4 vs. 2.0+/-0.3 ng/ml, P > 0.01). One hour after glucose challenge, the insulin level was significantly increased in the WKY rat (4.8+/-0.7 ng/ml) but not in the SHR (2.2+/-0.4 ng/ml). With L-NAME treatment, plasma insulin increase was noted in the WKY rat but not SHR (4.6+/-0.6 vs. 2.6+/-0.4 ng/ml, n = 8, P < 0.01). One hour after insulin 1 IU/kg was injected intramuscularly (i.m.), the plasma glucose level was significantly decreased in both the SHR (from 115.0+/-6.5 to 48.6+/-3.6 mg/dl, n = 8) and WKY rat (from 108.3+/-3.8 to 52.6+/-4.2 mg/dl, n = 8). No significant difference was noted between the decrease of the two groups (P > 0.01). The present findings suggested that NO plays a role in the glucose homeostasis of rats. NO-synthase blockade resulted in an increase of plasma glucose level. The SHR maintains normal glucose level and tolerance in spite of a defective insulin release response. This is probably due the compensatory effect of a more prominent NO-dependent glucose homeostatic function.

Animals↗