Bupivacaine Indirectly Potentiates Glutamate-induced Intracellular Calcium Signaling in Rat Hippocampal Neurons by Impairing Mitochondrial Function in Cocultured Astrocytes.

Background: Bupivacaine induces central neurotoxicity at lower blood concentrations than cardiovascular toxicity. However, central sensitivity to bupivacaine is poorly understood. The toxicity mechanism might be related to glutamate-induced excitotoxicity in hippocampal cells.

[Quantification of (-)doxazosin at very low concentration in rat plasma samples by SPE-LC-MS/MS].

Previous publications showed that the value of LLOQ (lowest limit of quantification) for doxazosin and its enantiomers in biological samples were above 0.1 ng·m L(-1). The present study was designed to establish a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification at very low concentration of (-)doxazosin in rat plasma after intravenous administration of (-)doxazosin（3.

Differential effects of short- and long-term bupivacaine treatment on α1-adrenoceptor-mediated contraction of isolated rat aorta rings and the reversal effect of lipid emulsion.

Aim: Arterial function is significantly influenced by bupivacaine at both clinically relevant concentrations and toxic concentrations, but the underlying mechanisms are not fully understood. In the present study we investigated the role of α1-adrenoceptors in bupivacaine effects on isolated rat aortas.

Methods: Isolated aortic rings were prepared from rats and suspended in an organ bath.

[An overview of effects of traditional medicine on pharmacokinetics of western medicine].

Traditional medicine (herb medicine) began to prevail again over last two decades, and it is about 70% of the world population taking herb medicine as supplement or alternative medicine according to a recent survey. The consumption of herb medicine increased exponentially in Canada, Australia and Europe during last 10 years. Since concomitant administration of herbal and western medicine has become a trend, it requires paying close attention to the problem.

Doxazosin selectively potentiates contraction to serotonin via 5-HT₂A receptors in longitudinal muscle strips of the rabbit gastric body.

The aims of this study were to examine the effects of doxazosin on contractile responses to 5-hydroxytryptamine (5-HT), carbachol, and histamine, and to compare them with those of prazosin, alfuzosin, and terazosin, and then characterize a pharmacological profile of the 5-HT-induced contractile response using preparations of isolated longitudinal muscle strips from the rabbit gastric body. The results from these preparations showed that the contraction response to 5-HT, but not to carbachol or histamine, was found to be dose-dependently potentiated by doxazosin and its enantiomers. The specific potentiation effect on 5-HT was not observed in the preparations that were treated with prazosin, terazosin, or alfuzosin.

(-)Doxazosin is a necessary component for the hypotensive effect of (±)doxazosin during long-term administration in conscious rats.

Aim: Doxazosin is a racemic mixture of (-)doxazosin and (+)doxazosin that is currently used as an add-on therapy for hypertension. In this study we investigated the contribution of each enantiomer to the hypotensive action of long-term administration of (±)doxazosin in conscious rats.

Methods: Blood pressure of conscious SD rats was measured using a volume pressure recording system.

Stereoselective binding of doxazosin enantiomers to plasma proteins from rats, dogs and humans in vitro.

Aim: (±)Doxazosin is a long-lasting inhibitor of α1-adrenoceptors that is widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms. In this study we investigated the stereoselective binding of doxazosin enantiomers to the plasma proteins of rats, dogs and humans in vitro.

Methods: Human, dog and rat plasma were prepared.

Berberine improves neurogenic contractile response of bladder detrusor muscle in streptozotocin-induced diabetic rats.

Ethnopharmacological Relevance: Coptidis Rhizoma has been used to treat diabetes mellitus for more than 1400 years in China. Berberine, one of the main alkaloids of Coptidis Rhizoma, is a principal antidiabetic component of Coptidis Rhizoma. To investigate the effects of berberine on impaired neurogenic contractility of detrusor muscle from urinary bladder of rats with early stage diabetes.

[Determination of doxazosin enantiomers in rat plasma and investigation of their chiral inversion].

The study is to establish an HPLC method using fluorescence detector for the determination of doxazosin enantiomers and investigate their chiral inversion in vitro and in vivo. Ultron ES-OVM was taken as the chiral chromatographic column, and the column temperature was 30 degrees C. Isocratic elution using a mobile phase of phosphate buffer-acetonitrile (85 : 15, v/v) at a flow rate of 0.

Chiral recognition of doxazosin enantiomers in 3 targets for therapy as well as adverse drug reactions in animal experiments.

Doxazosin used in benign prostatic hyperplasia has the side effects of causing hypotension and the risk of heart failure. The 3 targets of α(1A)-adrenoceptors (in the prostate), α(1D)-adrenoceptors (in the aorta), and an unknown mechanism (in the heart) are involved, respectively. We hypothesized that there is a chiral recognition of doxazosin enantiomers in the 3 targets.

Effects of imidazolines on neurogenic contraction in isolated urinary bladder detrusor strips from rabbit.

Moxonidine and clonidine, which are imidazoline compounds, are sympathetic modulators used as centrally acting antihypertensive drugs. Moxonidine, clonidine, and agmatine produce extensive effects in mammalian tissues via imidazoline recognition sites (or receptors) or α(2)-adrenoceptors. To investigate the effects of imidazolines on the function of the urinary bladder, we tested the effects of moxonidine, clonidine, and agmatine on the neurogenic contraction induced by electric field stimulation, and on the post-synaptic receptors in isolated urinary bladder detrusor strips from rabbit.

Exhaustive swimming differentially inhibits P2X1 receptor- and α1-adrenoceptor-mediated vasoconstriction in isolated rat arteries.

Aim: To investigate the effects of exhaustive swimming exercise on P2X1 receptor- and α1-adrenoceptor-mediated vasoconstriction of different types of arteries in rats.

Methods: Male Wistar rats were divided into 2 groups: the sedentary control group (SCG) and the exhaustive swimming exercise group (ESEG). The rats in the ESEG were subjected to a swim to exhaustion once a day for 2 weeks.

Relaxant and contractile responses of detrusor muscle strips obtained from bladder outlet-obstructed rats treated with doxazosin enantiomers.

(-)Doxazosin, one of (±)doxazosin enantiomers, was speculated to have a pharmacological enantioselectivity between the cardiovascular system and the urinary system by comparison with (+)doxazosin. Therefore, to evaluate the potential benefits of (-)doxazosin in the treatment of benign prostate hyperplasia, we compared the effects of the 3 agents, using rat mesenteric artery preparations and obstructed bladder strips. Concentration-response curves for carbachol (contractile response) and isoprenaline (relaxant response) in detrusor muscle strips of the bladder outlet obstruction (BOO) rats were shifted to the left, with significant increases in the Emax values, and significant decreases in the EC50 values by comparison with the sham-operated rats (P < 0.

Physiological significance of P2X receptor-mediated vasoconstriction in five different types of arteries in rats.

P2X(1) receptors, the major subtype of P2X receptors in the vascular smooth muscle, are essential for α,β-methylene adenosine 5'-triphosphate (α,β-MeATP)-induced vasoconstriction. However, relative physiological significance of P2X(1) receptor-regulated vasoconstriction in the different types of arteries in the rat is not clear as compared with α(1)-adrenoceptor-regulated vasoconstriction. In the present study, we found that vasoconstrictive responses to noncumulative administration of α,β-MeATP in the rat isolated mesenteric arteries were significantly smaller than those to single concentration administration of α,β-MeATP.

Pharmacologic characteristics of bladder micturition function in anesthetized mice.

In the present study, we observed the effects of an α(1)-adrenoceptor agonist (phenylephrine), β-adrenoceptor agonist (isoprenaline), muscarinic cholinoceptor agonist (carbachol), and α(1)-adrenoceptor antagonist (doxazosin) on the bladder micturition function in anesthetized mice. Changes in bladder pressure in response to filling and blood pressure were recorded by using a data acquisition system. Phenylephrine (50 to 800 μg/kg) increased vesical micturition pressure in a dose-dependent manner but increased micturition basal pressure only at 800 μg/kg.

[Effects of doxazosin and its enantiomers on serum lipid levels in rabbits fed by an atherogenic diet].

Objective: To observe the effects of (-)doxazosin(DOX), (+)DOX and (+/-)DOX on serum lipid levels and the mortality rates of the rabbits fed by an atherogenic diet.

Methods: Male white New Zealand rabbits were fed by an atherogenic diet for 4 weeks. 8 rabbits whose serum TC <10 mmol/L were confirmed as normal diet group and were fed normally.

Effects of (-)doxazosin on histomorphologic and cell apoptotic changes of the hyperplastic prostate in castrated rats.

Background: (-)Doxazosin is one of the enantiomers of (+/-)doxazosin, and it was reported that (-)doxazosin possessed higher selectivity for lower urinary tract between the cardiovascular system and the urinary system in the animal experiments in comparison with that of (+/-)doxazosin and (+)doxazosin. Therefore, it is important to know whether (-)doxazosin has a therapeutic effect on the hyperplastic prostate.

Methods: (-)Doxazosin and (+/-)doxazosin were administered intragastrically to prostatic hyperplasia rats, induced by testosterone propionate for 4 weeks, and each experimental group contained 8 animals.

[Pharmacological characteristics of contractile responses regulated by P2Y receptors in circular smooth muscle of the rat gastric body].

This study is to observe the difference in pharmacological characteristics between circular smooth muscles of rat isolated gastric body and gastric fundus, and to investigate the effects of nucleoside and nucleotide on circular smooth muscle of the rat gastric body and the involved receptors. Circular muscle strips of the rat gastric body and gastric fundus were prepared, and contractile responses to agonists were investigated with a technique of drug-receptor interaction in functional system. There was no significant difference between the circular muscle strips of the gastric body and gastric fundus in the responses to KCl, and no difference in EC50 values of contractile responses for 5-HT and His between the two kinds of preparations (P > 0.

Potentiation by yohimbine of alpha-adrenoceptor-mediated vasoconstriction in response to clonidine in the rabbit ear vein.

We investigated the pharmacological profile of the vasoconstrictive response to clonidine in the isolated rabbit ear vein, and compared the characteristics of clonidine with those of noradrenaline and moxonidine. The maximal vasoconstrictive responses to clonidine and moxonidine in the rabbit ear vein were 35.94+/-11.

[Effect of isosorbide-5-mononitrate on sympathetic purinergic vasoconstriction of the rabbit saphenous artery].

The aim of this study is to investigate the effect of isosorbide-5-mononitrate (ISMN) on the electric field stimulation induced sympathetic purinergic vasoconstriction of the rabbit saphenous arterial rings. Isometric vasoconstrictive responses to electric field stimulation and to exogenous noradrenaline and adenosine triphosphate were recorded. We found that the vasoconstrictive responses to electric field stimulation (15 V, 1 ms pulse duration, 2 - 16 Hz) were frequency-dependant in the rabbit saphenous arterial rings, and abolished by tetrodotoxin (0.

[Effects of doxazosin enantiomers on alpha-adrenoceptors of isolated rabbit blood vessels].

Doxazosin, a high selective alpha1-adrenoceptor antagonist, is considered as the first-line therapy for the patients with benign prostatic hyperplasia (BPH) and also produce several side effects in cardiovascular system. In this study, we observed the isometric vasoconstrictive responses of the rabbit isolated arterial rings to electric field stimulation and noradrenaline ( NA ) to study the effects of R-doxazosin ( R-DOX ) and S-doxazosin ( S-DOX ) on the alpha1-adrenoceptor-regulated vasoconstrictive responses in the rabbit isolated ear artery, mesenteric artery and pulmonary artery, and the effects of higher concentration of S-DOX and R-DOX on presynaptic alpha2-adrenoceptor-regulated purinergic vasoconstriction in the rabbit isolated saphenous artery. We found that R-DOX and S-DOX competitively inhibited the vasoconstriction induced by NA in the rabbit isolated ear artery, mesenteric artery and pulmonary artery.

Chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats.

Aim: To study chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats.

Methods: In anesthetized rats, the carotid blood pressure, left ventricular pressure of the heart and the urinary bladder pressure were recorded.

Results: Administration of S-doxazosin at 0.

Growth inhibitory effect and apoptosis induced by extracellular ATP and adenosine on human gastric carcinoma cells: involvement of intracellular uptake of adenosine.

Aim: To study the growth inhibitory and apoptotic effects of adenosine triphosphate (ATP) and adenosine (ADO) on human gastric carcinoma (HGC)-27 cells in vitro and the mechanisms related to the actions of ATP and ADO.

Methods: MTT assay was used to determine the reduction of cell viability. The morphological changes of HGC-27 cells induced by ATP or ADO were observed under fluorescence light microscope by acridine orange/ethidium bromide double-stained cells.

Inhibitory effects of extracellular adenosine triphosphate on growth of esophageal carcinoma cells.

Aim: To study the growth inhibitory effects of ATP on TE-13 human squamous esophageal carcinoma cells in vitro.

Methods: MTT assay was used to determine the inhibition of proliferation of ATP or adenosine (ADO) on TE-13 cell line. The morphological changes of TE-13 cells induced by ATP or ADO were observed under fluorescence light microscope by acridine orange (AO)/ethidium bromide (EB) double stained cells.