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C Han

Publications and source records attributed to C Han.

At least 163 records · Page 9Linked to original sources
PubMed1991

Calcitonin gene-related peptide (CGRP) causes endothelium-dependent cyclic AMP, cyclic GMP and vasorelaxant responses in rat abdominal aorta.

Calcitonin gene-related peptide (CGRP), a neuropeptide found in nerves surrounding most blood vessels, is a potent hypotensive agent in both humans and rats. In isolated strips of rat thoracic aorta, CGRP has been reported to cause endothelium-dependent relaxation. To study the cellular and molecular mechanisms involved in CGRP-induced vasodilation, we investigated the roles of two second messengers, cyclic AMP and cyclic GMP, as potential mediators of the signal transduction mechanism leading to vasodilation in response to CGRP in rat aorta. In the present study, the abdominal aorta, rather than thoracic aorta, was used because of its higher content of endogenous CGRP and, therefore, the greater likelihood of regulation by CGRP in vivo. Each abdominal aortic ring was precontracted with norepinephrine (NE) at its EC50 concentration (10-20 nM). CGRP (3-300 nM) caused concentration-dependent relaxations (reducing the NE-induced contractions by 34%) that were completely dependent on endothelium. The relaxations in response to CGRP were correlated in a time- and concentration-dependent manner with increases in aortic levels of both cyclic AMP and cyclic GMP. CGRP (100 nM) caused significant elevations of cyclic AMP levels (1.4 to 3.2 pmol/mg protein, at 1 min) and cyclic GMP levels (1.6 to 3.6 pmol/mg protein, at 30 s). Like the vasorelaxant responses, both cyclic AMP and cyclic GMP responses to CGRP were totally dependent on the endothelium. Pre-incubation with indomethacin (3 microM, 15 min) did not alter cyclic AMP responses to CGRP (100 nM), suggesting that prostaglandins are not involved. Therefore, CGRP-induced vasodilations of abdominal aorta involve an endothelium-dependent mechanism associated with cyclic GMP elevations, similar to the mechanisms of vasodilation in response to acetylcholine and other endothelium-dependent vasodilators. However, CGRP-induced relaxations of aorta involve an additional mechanism (i.e., endothelium-dependent cyclic AMP elevations), which may also contribute to the intracellular mechanism of aortic vasodilation in response to CGRP.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Calcitonin gene-related peptide (CGRP)-induced cyclic AMP, cyclic GMP and vasorelaxant responses in rat thoracic aorta are antagonized by blockers of endothelium-derived relaxant factor (EDRF).

The mechanism of CGRP-induced vasodilation in rat thoracic aorta was investigated using antagonists of the classical endothelium-derived vasorelaxant factor (EDRF) and comparisons with acetylcholine-induced vasodilations. The CGRP-induced relaxations of isolated rings of rat thoracic aorta were completely dependent on the presence of endothelium and were associated with increases in the levels of both cyclic AMP and cyclic GMP, the same as in our previous study using rat abdominal aorta. Maximum relaxations to CGRP, which represented 40-50% reversal of the norepinephrine-induced contractions, occurred with 100 nM CGRP. Addition of acetylcholine (ACh, 1 microM) to aortic rings, which were already maximally relaxed to CGRP, caused further relaxation to 100%, suggesting that CGRP may use a mechanism (or pool of EDRF) different from that of ACh. Both CGRP- and ACh-induced relaxations of aorta were significantly inhibited by the EDRF blocking agents, hemoglobin (10 microM), methylene blue (10 microM), and nordihydroguaiaretic acid (NDGA, 10 microM). In fact, hemoglobin and NDGA were more effective as inhibitors of CGRP-induced relaxations than ACh-induced relaxations. Hemoglobin, methylene blue and NDGA also inhibited the CGRP-induced increases in both cyclic AMP and cyclic GMP levels. On the other hand, indomethacin, a cyclo-oxygenase inhibitor, did not alter CGRP-induced vasorelaxations or increases in either cyclic AMP or cyclic GMP levels, suggesting that prostaglandins are not involved. Therefore, CGRP-induced vasodilations in rat thoracic aorta appear to involve EDRF, leading to cyclic GMP elevations in smooth muscle and ultimately vasorelaxations. However, another previously undescribed mechanism, which involves EDRF-dependent and indomethacin-resistant elevations of cyclic AMP levels, is triggered by CGRP in thoracic aorta. This novel EDRF-dependent cyclic AMP response may contribute to the CGRP-induced vasodilation in rat thoracic aorta.

Acetylcholine↗
PubMed1991

[Prevention of in vivo formation of NMBz A and the formation of oesophageal tumour by tea in rats].

Five groups of rats (22 per group) were intubated with precursors of N-Nitrosomethylbenzylamine (NMBzA), i.e. methylbenzylamine (1 mmol/kg) and sodium nitrite (0.5 mmol/kg), and five varieties of Chinese tea. One positive control group was intubated with precursors of NM2A without tea and one negative control group with tap water and sodium nitrite. After 12 week's treatment, significantly less lesions and papillomas in esophageal mucosa, examined by naked eye or by microscope, were found in the tea-treated groups than in the non-tea-treated positive control group. The results confirmed the anti-tumour ability of Chinese tea by blocking the in vivo formation of NMBzA in rats.

Animals↗
PubMed1991

Chinese tea inhibits the occurrence of oesophageal tumours induced by N-nitrosomethylbenzylamine and blocks its formation in rats.

Chinese tea can inhibit the occurrence of oesophageal tumours not only by blocking the formation of N-nitrosomethylbenzylamine (NMBzA) in vivo, but also by inhibiting the carcinogenesis of preformed NMBzA. The incidence of oesophageal tumours in rats intubated with preformed NMBzA (5 mg/kg bw per week) and with the precursors of NMBzA (methylbenzylamine, 1 mM/kg bw; nitrite, 0.5 mM/kg bw) without Chinese tea was higher than in tea-treated groups; the same tendency was found with regard to the severity of the oesophageal lesions. The anticarcinogenic effects of five varieties of Chinese tea were different from one another.

Animals↗
PubMed1990

Subtypes of alpha 1-adrenoceptors in rat blood vessels.

Two alpha 1-adrenoceptor subtypes (alpha 1A and alpha 1B) have been distinguished by competitive antagonists and the alkylating agent chloroethylclonidine. The chloroethylclonidine-insensitive subtype (alpha 1A) has been suggested to selectively activate Ca2+ influx through dihydropyridine-sensitive channels in smooth muscle. We compared the effects of chloroethylclonidine and nifedipine on contractile responses to norepinephrine (NE) in rat blood vessels. Pretreatment with chloroethylclonidine caused a large shift to the right and decrease in maximum for NE-induced contractions of rat aorta, however, nifedipine had no effect in this tissue. Chloroethylclonidine had no effect on NE-induced contractions of rat renal arteries, which were almost completely abolished by nifedipine. Both chloroethylclonidine and nifedipine partially attenuated NE-induced contractions in rat mesenteric artery and portal vein. Addition of nifedipine abolished residual contractions remaining after chloroethylclonidine pretreatment in all four types of vessels. The pA2 for the competitive antagonist WB 4101 was highest in renal artery and lowest in aorta. These results suggest that the sensitivity of rat blood vessels to chloroethylclonidine is inversely related to their sensitivity to nifedipine, and support the existence of two alpha 1-adrenoceptor subtypes in rat blood vessels. Rat aorta appears to contain primarily alpha 1B receptors, renal artery primarily alpha 1A, and mesenteric artery and portal vein mixtures alpha 1A of and alpha 1B.

Animals↗
PubMed1990

[Use of 2H-labeled compound and GC-MS in the isolation and identification of a metabolite of biphenyldimethyl-dicarboxylate in rat urine].

Dimethyl-4, 4'-dimethoxy-5, 6, 5', 6'-dimethylenedioxy-biphenyl-2, 2'-dicarboxylate (biphenyldimethyldicarboxylate; BDD), a synthetic compound, has been used in the treatment of chronic hepatitis with good results in reducing s-GPT. Previous work in our laboratory studied its metabolites using 3H-labeled compound in combination with TLC and found that its main metabolic pathway is demethylation followed by conjugation with glucuronic acid. This paper reports the isolation and identification of a metabolite of BDD from rat urine using 2H-labeled compound and GC-MS. Rats fasted for 12 h were intragastrically given a mixture of 2H-labeled (consisting of monodeutero- and dideutero-BDD in the ratio about 1:1.3) and non-labeled BDD 150 mg/kg and placed in metabolism cages for urine collection. The 24 h urine was filtered and extracted three times each with 5 ml of methylenedichloride. The extracts were pooled and evaporated to dryness under reduced pressure at 35 degrees C. The residue was redissolved in chloroform and subjected to GC-MS analysis. The mass spectrum (m/z: 404, 405, 406; 373, 374, 375; 345, 346, 347; 330, 331, 332; etc) indicates that the molecular ionic and fragment peaks of the metabolite all have 14 amu less than those of BDD. This means that the metabolite isolated is mono-O-demethylated BDD. The result confirmed our findings reported previously.

Animals↗
PubMed1990

The effect of Chinese tea on occurrence of esophageal tumor induced by N-nitrosomethylbenzylamine in rats.

Five groups of rats (40 rats per group) were given five different varieties of Chinese tea (1 g/50 ml) and another two groups of rats (a positive control and a negative control) were given tap water as drinking water. Except for the negative control group, all the animals were intubated with N-nitrosomethylbenzylamine (NMBzA, 5 mg/kg body wt/week). Half of the animals in each group were sacrificed after 6 weeks and the remaining animals at the end of 12 weeks. The incidences of esophageal mucosa lesions (16-59%) at the end of 6 weeks were significantly lower in the tea-treated rats than in the positive control group (100%). The incidences of esophageal tumor at the end of 12 weeks (42-67%) were also significantly lower in the tea-treated groups than in the positive control group (90%). The same phenomenon was found with respect to the size and number of tumors in each tumor-bearing animal. The relative anticarcinogenic effects of the five varieties of Chinese tea were different. The Fujian oolong tea and jasmine tea exhibited the strongest effects. The results suggest that Chinese tea can effectively inhibit the carcinogenesis caused by an N-nitroso compound.

Animals↗
PubMed1989

Changes in cardiac neuropeptide Y after experimental myocardial infarction in rat.

We have investigated the hypothesis that neuropeptide Y (NPY) is released from noradrenergic sympathetic nerves during experimentally induced myocardial infarction. A left thoracotomy was performed, the left main coronary artery ligated, and the animals sacrificed 4 or 48 h later. NPY levels in heart tissue from these rats and sham-operated controls were measured with radioimmunoassay. Levels of NPY in the right atrium were greater than other regions of the rat heart. After ligation of the left coronary artery, the concentration of NPY in the infarcted area of the left ventricle was reduced at 4 and 48 h when compared to a similar area in sham-operated rats. NPY levels in the septum were unchanged. The results suggest that during myocardial infarction, NPY is released from nerves in the infarcted region and may deleteriously affect increased collateral blood flow surrounding the infarcted tissue.

Animals↗
PubMed1989

Direct observations of ligand dynamics in hemoglobin by subpicosecond infrared spectroscopy.

The photodissociation of CO from HbCO at ambient temperature is studied by means of a femtosecond IR technique. The bleaching of the FeCO absorption and the appearance of a new IR absorption near that of free CO are both observed at 300 fs after optical excitation. The bleach does not recover on the time scale of a few picoseconds but does recover by approximately 4% within 1 ns, which suggests that a barrier to recombination is formed within a few picoseconds. The CO spectrum does not change significantly between 300 fs and 1 ns, suggesting that the CO quickly finds some locations in the heme pocket that are not more than a few angstroms from the iron. The de-ligated CO appears in its ground vibrational level. There is evidence that 85 +/- 10% of this CO remains in the heme pocket at 1 ns; it probably resides there for 50 ns. The flow of excess vibrational energy from the heme to the solvent was directly observed in the IR experiments. The heme cools within 1-2 ps while thermal disruption of the surrounding solvent structure requires approximately 30 ps.

Carboxyhemoglobin↗
PubMed1989

Effects of neuropeptide Y on contraction, relaxation, and membrane potential of rabbit cerebral arteries.

The effects of porcine neuropeptide Y (NPY) on agonist-induced contraction, relaxation, and intracellular membrane potential were studied in isolated ring segments of rabbit cerebral arteries. NPY caused contraction of cerebral arteries with a mean EC50 of 2.7 +/- 0.07 nM. After exposure of cerebral arteries to 1.5 nM NPY, the potencies of norepinephrine (NE) and histamine in causing contraction were increased by approximately twofold, with no change in maximal contraction. In cerebral arteries contracted with histamine, adenosine, and acetylcholine-induced relaxation was inhibited by 7-14-fold in the presence of 1.5 nM NPY, with no change in maximal relaxation. These effects of NPY were not altered by sympathetic denervation of cerebral arteries. Intracellular membrane potential in smooth muscle cells of cerebral arteries was measured using glass microelectrodes and averaged -66 +/- 1 mV. NPY 3 nM, ouabain 3 microM, and K+ Krebs solution 1 mM depolarized cerebral arteries by 15, 22, and 14 mV, respectively. In arteries depolarized by ouabain or 1 mM K+ Krebs solution, 3 nM NPY caused no additional depolarization. The potency of NE in causing contraction of cerebral arteries was increased by 3 microM ouabain (3.8-fold) and 1 mM K+ Krebs solution (1.9-fold); however, 3 nM NPY in the presence of ouabain or 1 mM K+ Krebs solution caused no greater increase in agonist potency. Ouabain 3 microM inhibited adenosine-induced relaxation by 5.1-fold whereas addition of 3 nM NPY to ouabain exposed arteries caused an additional 4.6-fold inhibition of relaxation. Ouabain and ouabain plus NPY also decreased the maximal relaxant effect of adenosine. These results suggest that the ability of NPY to potentiate contraction and inhibit relaxation of cerebral arteries is caused, at least in part, by NPY-induced membrane depolarization.

Acetylcholine↗
PubMed1989

[Analysis of 38 cases with epilepsy in forensic psychiatric evaluation].

Analysing 38 cases with epilepsy in forensic psychiatric evaluation shown that violence behavior were frequently seen, especially significant difference in psychomotor epilepsy in comparison with the other typical epilepsy (0. 01), and that epileptic psychopathy were frequently seen in intermission. Authors dealt with criminal responsibility in epileptic psychopathy.

Adult↗
PubMed1989

[The effect of Chinese teas on the occurrence of oesophageal tumor caused by N-nitrosomethylbenzylamine in rats].

Five groups of rats were given different varieties of Chinese tea as drinking water and on additional two groups of rats were given water with or without N-nitrosomethylbenzylamine (NMBzA) as controls. Except the control group, all the animals were intubated with NMBzA (5 mg.kg-1/wk) for 6 or 12 weeks. After 6 weeks, the incidence of oesophageal mucosa lesions was significantly lower in the tea-treated rats (16-59%) than the control group with NMBzA (100%). After 12 weeks, the incidence of oesophageal tumor was also significantly lower in the tea-treated groups (42-67%) than the control group with NMBzA (90%). Similar results were obtained in the tumor size and the number of tumors developed. The anti-carcinogenic effects of the 5 varieties of Chinese tea were also not the same the Fujian Oolong tea and Jasmine tea had the strongest effect. The results suggest that Chinese tea can inhibit the carcinogenesis caused by N-nitroso compound.

Animals↗
PubMed1988

Neuropeptide Y: vasoconstrictor effects and possible role in cerebral vasospasm after experimental subarachnoid hemorrhage.

The possible role of neuropeptide Y (NPY) as a vasoconstrictor substance contributing to the development of cerebral vasospasm after experimental subarachnoid hemorrhage was studied. Autologous blood was injected into the cisterna magna of control rabbits and rabbits that had received bilateral superior cervical ganglionectomy 2 days before blood injection. Three days after blood injection the concentration of NPY in cerebrospinal fluid (CSF) was 5971 +/- 551 pg/ml while CSF from control animals contained 992 +/- 162 pg/ml of NPY. The effects of porcine NPY on norepinephrine-induced contraction of rabbit cerebral arteries were also studied in vitro. NPY (1.2 nM) caused a 3-fold potentiation of norepinephrine-induced contraction of cerebral arteries. CSF from control rabbits diluted by 50% with Krebs solution had no significant effect on norepinephrine-induced contraction of cerebral arteries when compared to responses in Krebs solution only; however, diluted CSF from denervated blood-injected rabbits potentiated norepinephrine-induced contraction by 2.6-fold. Antiserum containing NPY specific antibodies was used to immunoprecipitate the peptide from CSF taken from denervated blood-injected rabbits. CSF treated with this antiserum contained less than 40 pg/ml of NPY and had no effect on norepinephrine-induced contraction of cerebral arteries. These results show that the concentration of NPY in CSF of rabbits is elevated after experimental subarachnoid hemorrhage. In addition, NPY in CSF can potentiate the vasoconstrictor effect of norepinephrine which may contribute to the development of cerebral vasospasm.

Animals↗
PubMed1988

High levels of NPY in rabbit cerebrospinal fluid and immunohistochemical analysis of possible sources.

We have analyzed rabbit cerebrospinal fluid for neuropeptide Y (NPY)-like immunoreactivity, using high performance liquid chromatography (HPLC) and radioimmunoassay (RIA) and examined the anatomical relationship of NPY-containing fibers to the cerebral vasculature and the third cerebral ventricle. Cerebrospinal fluid (CSF) obtained from the cisterna magna of rabbits was injected into a C18 column and subjected to HPLC. The fractions were collected, dried and reconstituted in buffer for NPY radioimmunoassay. A single peak of NPY immunoreactivity was obtained which corresponded in retention time to synthetic porcine NPY. Analysis of CSF samples produced displacement curves parallel to the standard curve. Immunohistochemistry revealed numerous NPY-labeled fibers which penetrated the ependymal lining of the third cerebral ventricle and directly bordered the ventricular lumen. Other fibers were observed in the pia which lines the ventral aspect of the hypothalamus. The basilar artery, its branches and other cerebral vessels were surrounded by NPY-labeled fibers. The results show that: (1) approximately 1 ng/ml of NPY immunoreactivity which corresponds chromatographically to synthetic porcine NPY is present in rabbit CSF; (2) NPY-containing fibers surround the basilar artery and other cerebral vessels; (3) NPY may be released into the CSF from axons in the pia and from axons which penetrate the ependymal lining of the third ventricle. These observations form the basis for our analysis of the vasoconstrictor effects of NPY and its role in cerebrovasospasm after experimental subarachnoid hemorrhage.

Animals↗
PubMed1988

Comparison of alpha 1-adrenergic receptor subtypes distinguished by chlorethylclonidine and WB 4101.

We showed previously that subtypes of alpha 1-adrenergic receptors can be differentiated by selective inactivation with chlorethylclonidine (CEC) [Mol. Pharmacol. 32:505-510 (1987)] or by their affinities for the competitive antagonist WB 4101 [Nature (Lond.) 329:333-335 (1987)]. Examining eight rat tissues, the proportions of 125IBE 2254-binding sites sensitive to inactivation by CEC correlated significantly (p less than 0.05) with the proportion having a low affinity for WB 4101. However, the proportion of CEC-sensitive sites was always smaller than the proportion of low affinity WB 4101 sites. Further experiments showed that repetitive pretreatment with CEC or pretreatment under hypotonic conditions caused a larger inactivation of binding sites, suggesting that CEC did not access all sites under the isotonic conditions used previously. The proportions of binding sites inactivated by 10 microM CEC under hypotonic conditions were quantitatively similar to and correlated significantly (p less than 0.01) with the proportion having a low affinity for WB 4101. Pretreatment of hippocampus and vas deferens with CEC caused a loss of all low affinity WB 4101-binding sites, leaving only high affinity sites. In vas deferens, CEC pretreatment decreased the potency of norepinephrine in stimulating 3H-inositol phosphate accumulation but not contractile responses. In rat liver slices, CEC inactivated norepinephrine-stimulated 3H-inositol phosphate accumulation in parallel with 125IBE-binding sites. These results suggest that: 1) the CEC-sensitive and -insensitive 125IBE 2254-binding sites are equivalent to those with a low and high affinity for WB 4101, respectively, and 2) the CEC-sensitive binding sites with a low affinity for WB 4101 are the alpha 1-adrenergic receptors linked to inositol phospholipid hydrolysis.

Animals↗