Carthamus tinctorius L. is a traditional Chinese medicine with the effect of promoting blood circulation and removing blood stasis. HSYA (hydroxysafflor yellow A) is the main effective component of Carthamus tinctorius L. In order to study the inhibitory effects of HSYA against PMN (polymorphonuclear) activation induced by LPS (lipopolysaccharide), rabbit PMN adhesion potency which was activated by LPS through colorimetry method was observed. Cellular free calcium concentration was determined by fluorescence spectrophotometry. RT-PCR was applied to study the effect of HSYA on PMN TNF-alpha and IL-6 mRNA expression; The inhibition of HSYA on NF-kappaB activation was monitored with immunofluorescence. The results showed that after treated with HSYA, the increase of adhesion potency (HSYA dose 1.01 x 10(-4) mol x L(-1)), free calcium concentration (HSYA dose 3.1 x 10(-5) mol x L(-1)), TNF-alpha and IL-6 mRNA expression elevation (HSYA dose 5.2 x 10(-1) mol x L(-1)) induced by LPS were inhibited. HSYA can inhibit NF-kappaB p65 subgroup nuclear translocation (HSYA dose 5.2 x 10(-5) mol x L(-1)). It is suggested that HSYA is effective in PMN activation induced by LPS.

This study is to investigate the pharmacological effect and mechanism of action of hydroxysafflor yellow A (HSYA) on acute lung injury (ALI). The rat ALI was induced by oleic acid and lipopolysaccharide (LPS) injection. The incidence of acidosis, PaO2 (arterial blood oxygen pressure), W/D (wet weight/dry weight) and lung index (LI) were measured. Electron microscope and optical microscope were applied to observe lung morphological changes in rat. RT-PCR was used to determine TNF-alpha and ICAM-1 mRNA level. Inhibition effect of HSYA on plasma inflammatory cytokine expression was measured by ELISA. HSYA could alleviate pulmonary edema, reduce acidosis, keep PaO2 from descending, inhibit inflammatory cell infiltration, inhibit rat lung TNF-alpha and ICAM-1 mRNA expression and plasma IL-6 and IL-1beta level elevation. HSYA is an effective ingredient to remit ALI induced by oleic acid and LPS in rat.

Using whole-cell patch clamp technique this study investigated the effects of adenosine (Ado) on action potential, L-type calcium current (I(Ca.L)), delayed afterdepolarizations (DADs), and transient inward current (I(ti)) induced by isoproterenol (Iso) in guinea pig isolated single ventricular myocytes. The results showed: (1) Ado alone had no significant direct effects on action potential and I(Ca.L) in guinea pig ventricular myocytes at 20-100 micromol/L. However, Ado significantly attenuated the prolongation of action potential duration (APD) and the increase of the peak amplitude of I(Ca.L) induced by Iso. Iso (10 nmol/L) markedly increased APD(50) and APD(90) from 340+/-21 ms to 486+/-28 ms and from 361+/-17 ms to 501+/-29 ms, respectively (P<0.01), and increased the amplitude of I(Ca.L) from 6.53+/-1.4 pA/pF to 18.28+/-2.4 pA/pF (P<0.01). The peak potential of current-potential relationship shifted to the left. Ado (50 micromol/L) abbreviated APD(50), APD(90) to 403+/-19 ms and 419+/-26 ms (P<0.01), and decreased the peak amplitude of I(Ca.L) to 10.2+/-1.5 pA/pF (P<0.01 vs Iso), but did not change resting membrane potential (RMP), action potential amplitude (APA), and overshoot (OS). (2) Iso (30 nmol/L) reproducibly elicited DADs with 100% incidence of DADs under this condition. Ado (50 micromol/L) completely inhibited Iso from inducing DADs. Iso (30 nmol/L) elicited I(ti) with 2-second depolarizing voltage-clamp pulses rising to +20 mV from a holding potential of -40 mV, the incidence of I(ti) being 100%, and the I(ti) was suppressed in the presence of Ado (50 micromol/L) with the incidence of I(ti) decreased to 14.3% (P<0.05). These data indicate that Ado antagonizes the stimulatory effect of Iso, and that the antiarrhythmic mechanism of Ado preventing Iso-induced DADs is due to the inhibition of intracellular Ca(2+) overload through attenuating the prolongation of APD, the enhance of I(Ca.L) and I(ti).
Action Potentials ; drug effects ; Adenosine ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrhythmias, Cardiac ; physiopathology ; Calcium Channels, L-Type ; drug effects ; Female ; Guinea Pigs ; Heart Ventricles ; cytology ; Isoproterenol ; antagonists & inhibitors ; Male ; Myocytes, Cardiac ; physiology ; Patch-Clamp Techniques

The purpose of this study was to investigate the different effects of ACh on the action potential and force contraction in guinea pig atrial and ventricular myocardium by using standard microelectrodes and force transducer. The results showed that the duration of the action potential (APD) of atrial myocardium was shortened from 208.57+/-36.05 to 101.78+/-14.41 ms (n=6, P<0.01), and the APD of the ventricular myocardium was shortened from 286.73+/-36.11 to 265.16+/-30.06 ms (n=6, P<0.01).The amplitude of the action potential (APA) of the atrial myocardium was decreased from 88.00+/-9.35 to 62.62+/-20.50 mV (n=6, P<0.01), while the APA of the ventricular myocardium did not change significantly.The force contraction of atrial myocardium was inhibited completely (n=6, P<0.01), while the force contraction of ventricular myocardium was inhibited by 37.57+/-2.58% (n=6, P<0.01). The ACh effects correlated with its concentration. The K(D) of the APD shortening effects in the atrial and ventricular myocardium were 0.275 and 0.575 micromol/L. The K(D) of the negative inotropic in the atrial and ventricular myocardium were 0.135 and 0.676 micromol/L, respectively. The corresponding data points were compared using t test between the atrial and ventricular myocardium, and the differences were significant when the ACh concentration was above 10 nmol/L. Furthermore, atropine (10 micromol/L) and CsCl (20 mmol/L) blocked the effects of 10 micromol/L ACh on the APD of ventricular myocardium, while CdCl2 (0.1 mmol/L) had no influence on these effects. In conclusion, ACh could shorten the action potential duration and inhibit the force contraction of atrial and ventricular myocardium in a concentration-dependent manner. There are differences in the effects of ACh on the atrial and ventricular myocardium. The atrial myocardium is more sensitive to ACh than the ventricular myocardium. It is probable that the muscarinic receptor and the potassium channel, but not the calcium channel, are involved in the ACh-induced shortening of the ventricular APD.
Acetylcholine ; pharmacology ; Action Potentials ; drug effects ; Animals ; Calcium Channels ; metabolism ; Guinea Pigs ; Heart Atria ; drug effects ; Heart Ventricles ; drug effects ; Microelectrodes ; Potassium Channels ; metabolism ; Receptors, Muscarinic ; metabolism

OBJECTIVETo investigate the effect of isopropyl 3-(3,4-dihydroxyphenyl)-2- hydroxypropanoate on vascular smooth muscle.

METHODIsolated rat pulmonary artery was perfused and the tension of the vessel was measured, the effect of isopropyl 3-(3, 4-dihydroxyphenyl)-2-hydroxypropanoate on the pulmonary artery precontracted by noradrenaline (NE) and concentration-response curves of 5-hydroxytryptamine (5-HT), endothelin-1 (ET-1), U46619 and KCl was also observed.

RESULTIsopropyl 3-(3,4-dihydroxyphenyl) -2-hydroxypropanoate exerted relaxation effect on the endothelium-intact artery precontracted by NE in a concentration-dependent manner, which was inhibited with denuded endothelium. The right-shift of the concentration-response curves of 5-HT, ET-1, U46619 and KCl.

CONCLUSIONIsopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate have relaxation action on rat pulmonary artery in the way of endothelium-dependance, the mechanism of relaxation action by isopropyl 3-(3,4-dihydroxyphenyl) -2-hydroxypropanoate may be related to calcium channels.

Animals ; Female ; In Vitro Techniques ; Male ; Muscle Contraction ; drug effects ; Muscle, Smooth, Vascular ; drug effects ; physiology ; Propionates ; pharmacology ; Pulmonary Artery ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley

The gating mechanism of ClC-1 chloride channel was studied in this paper by heteroexpression of rat wild type ClC-1 gene in Xenopus oocytes and by two-electrode voltage clamping technique. The deactivation gating kinetic parameters were obtained by applying two exponential fitting of the deactivating currents at various extracellular chloride concentrations. It was found that decrease in extracellular chloride concentration increased the fractional amplitude of fast deactivating component, and depressed the fractional amplitude of slow deactivating component accompanied by a decrease in fast and slow deactivating time constants. These results demonstrate that the deactivation kinetic parameters of ClC-1 are largely dependent on the extracellular chloride concentration, which induces changes in channel gating.
Animals ; Chloride Channels ; drug effects ; physiology ; Chlorides ; pharmacology ; Electrophysiology ; Female ; In Vitro Techniques ; Ion Channel Gating ; drug effects ; physiology ; Oocytes ; physiology ; Rats ; Xenopus

To improve the differential diagnosis of sellar region mass,4 cases with sellar mass and misdiagnosed as lymphocytic hypophysitis (LYH) were reviewed retrospectively.The 4 patients (2 male and 2 female) aged 20-60 years old were all presented with symptoms of headache,polydipsia and polyuria.Biochemical studies confirmed the diagnoses of central diabetes insipidus and hypopituitarism.Head MRI scans showed LYH like image for all the cases,and,thus,high dose methylprednisolone pulse therapy (HDMPT) was applied to the patients.Their symptoms deteriorated and the sellar mass enlarged after a short period of partial improvement.Operations were performed in all the patients.Histology study showed craniopharyngioma with abscess,primary abscess,secondary hypophysitis caused by Wegener's granulomatosis,and germinoma with secondary hypophysitis,respectively.In conclusion,surgery or biopsy is necessary for those who presented with sellar region mass and was suspected to be with LYH,but with poor response or even worse after HDMPT.

The recent discovery of ischemic postconditioning is a landmark of anti-reperfusion injury. The medical community has a preference for postconditioning because it is easier to control in clinic and has reliable benefits to heart compared with preconditioning. Postconditioning is defined as a series of brief mechanical interruptions of blood flow applied at the very onset of reperfusion. It can reduce irreversible post-ischemic injury and protect myocardium. There are two important factors in the algorithm of postconditioning: cycle number and duration of intermittent episodes. The latter may depend on species and is more important than cycle number. Postconditioning-induced infarct-sparing effect persists not only after the acute phase of reperfusion but also after a prolonged reperfusion. However, whether cardioprotection of postconditioning is related to preservation of endothelial function and attenuation of oxidative damage is still under debate. Up-regulating the reperfusion injury salvage kinase (RISK) pathway is one of the most important mechanisms in cardioprotection of postconditioning, including activation of phosphatidylinositol 3-kinase (PI3K)-Akt and/or extracellular signal-regulated kinase (ERK), which reduces apoptosis and necrosis by inhibiting the opening of mitochondrial permeability transition pore (mPTP). But the signal transduction of these two pathways needs further research. In order to be more suitable for clinical application, researchers translate mechanical maneuver into drug intervention to investigate whether drug can simulate ischemic postconditioning in cardioprotection, termed pharmacological postconditioning. Adenosine is one of the most extensive and prospective drugs in pharmacological postconditioning study. However, in our laboratory we demonstrate that acetylcholine is able to induce pharmacological postconditoning through mitochondrial ATP-sensitive potassium channel. The present article reviews the protective effects and signal transduction of postconditioning, especially the mechanisms and clinical application of adenosine- and acetylcholine-induced pharmacological postconditioning.
Acetylcholine ; Adenosine ; Extracellular Signal-Regulated MAP Kinases ; Heart ; Humans ; Ischemic Postconditioning ; KATP Channels ; Mitochondrial Membrane Transport Proteins ; Myocardial Reperfusion Injury ; Myocardium ; Phosphatidylinositol 3-Kinases ; Potassium Channels ; Prospective Studies ; Proto-Oncogene Proteins c-akt ; Reperfusion Injury ; Signal Transduction

AIMTo observe the antagonistic effect of hydroxysafflor yellow A (HSYA) on the platelet activating factor (PAF).

METHODSWashed rabbit platelet (WRP) aggregation and rabbit polymorphonuclear leukocytes (PMNs) aggregation induced by PAF were observed by turbidimetric assay in vitro. The PAF receptor antagonistic effect of HSYA was investigated by radio ligand binding assay (RLBA).

RESULTSIn RLBA the specific binding inhibition effect of HSYA was found to be concentration-dependent in three different [3H]PAF concentrations. In the experiments, WRP aggregation and rabbit PMNs aggregation induced by PAF (9.55 x 10(-10), 9.55 x 10(-6) mol.L-1) were both inhibited by HSYA in a concentration-dependent manner in vitro. The IC50 of HSYA to inhibit WRP and rabbit PMNs aggregation was 0.99 and 0.70 mmol.L-1, respectively.

CONCLUSIONThe PAF receptor binding can be antagonized by HSYA.

Animals ; Carthamus ; chemistry ; Cell Aggregation ; drug effects ; Chalcone ; analogs & derivatives ; isolation & purification ; pharmacology ; In Vitro Techniques ; Male ; Neutrophils ; drug effects ; Plants, Medicinal ; chemistry ; Platelet Aggregation ; drug effects ; Platelet Membrane Glycoproteins ; antagonists & inhibitors ; Quinones ; isolation & purification ; pharmacology ; Rabbits ; Receptors, G-Protein-Coupled ; antagonists & inhibitors

Hypertension is a common cardiovascular disease and can induce many complications, such as stroke and coronary heart disease. The purpose of the present study was to investigate the effect of ischemia/hypoxia on mesenteric artery vasomotor function in spontaneously hypertensive rats (SHR). Rat mesenteric arterial rings were cultured in modified ischemia-mimetic solution in a hypoxia incubator for a certain time period. Isometric tension changes of isolated mesenteric arterial rings were recorded continuously by a myograph system. The results obtained were as follows: In SHR group, the maximum contractions to KCl and phenylephrine (PE) were increased, and the maximum relaxation to acetylcholine (ACh) was decreased, compared to those in Wistar-Kyoto (WKY) rats group. Compared with SHR group and WKY with acute ischemia/hypoxia (WKY+H) group, SHR with acute ischemia/hypoxia (SHR+H) increased the maximum contractions induced by KCl and PE and inhibited the maximum relaxations by ACh. In SHR+H and SHR groups, the vasodilation induced by ACh was unaffected by N(G)-nitro-L-arginine methylester (L-NAME), whereas in WKY group, the relaxation to ACh was attenuated by L-NAME. CaCl2-induced contraction in depolarized rings in SHR+H group significantly shifted to the left compared with SHR group. In Ca(2+)-free K-H solution, the maximum contractions induced by PE and caffeine were increased in SHR+H group compared to those in WKY+H group; the PE- and caffeine-induced contractions were also enhanced in SHR group versus WKY group; the maximum contraction induced by PE was significantly increased in SHR+H group versus SHR group. These findings suggest that acute ischemia/hypoxia aggravates mesenteric artery dysfunction in SHR. The mechanism may be related to the decreased NO generation and increased sarcoplasmic reticulum Ca(2+) release.
Animals ; Calcium ; metabolism ; Endothelium, Vascular ; metabolism ; physiopathology ; Hypertension ; physiopathology ; Hypoxia ; physiopathology ; In Vitro Techniques ; Male ; Mesenteric Arteries ; physiopathology ; Muscle, Smooth, Vascular ; physiopathology ; Nitric Oxide ; biosynthesis ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Vasomotor System ; physiopathology