OBJECTIVEUsing an experimental model of animals exposed to cold to evaluate the regulative effects of prazosin hydrochloride (Pra) and racanisodamine (Ani) on extremital skin temperature of rats and mice.

METHODSEighty animals were randomly divided into eight groups according to the drug dosage. After been administered with drugs by intragastric at room temperature for 60 min, the animals were moved into specified temperature (5 degrees C,18 degrees C) environment and the skin temperatures at the 1/3 site at the proximal end of tail were measured by infrared camera on 180 min and 300 min. Effects of drug were evaluated by changes in tail skin temperatures.

RESULTSPra and Ani combination raised the extremital skin temperature of experimental animals significantly in a dose-dependent manner, while single use of Pra was not potent to rats and less potent to mice, and single use of Ani could not raise extremital skin temperature of both rats and mice. Change of rectal temperature in mice showed that Pra and Ani combination did not affect core temperature.

CONCLUSIONPra and Ani combination could significantly raise extremital skin temperature of rats and mice exposed to cold, and would not affect their core (rectal) temperature.

Animals ; Body Temperature ; Cold Temperature ; Mice ; Prazosin ; pharmacology ; Rats ; Skin Temperature ; drug effects ; Solanaceous Alkaloids ; pharmacology

OBJECTIVETo investigate the changes of vasoconstriction and vasodilatation under different temperature conditions and the protective effects of Vitamin E (Vit E) against endothelial injury induced by hypothermia.

METHODSThe tail arterial rings were prepared for isometric tension recording using multi wire myograph system. The effect of temperature on relaxation and construction was evaluated. Incubate the arterial rings with different concentration of Vit E when they were exposed to hypothermia, then acetylcholine (ACh)-induced endothelium-dependent relaxation was investigated to evaluate the activity of endothelial.

RESULTS(1) The hypothermia could enhanced the dose-dependent construction induced by PE in mice tail artery. (2) Exposure to hypothermia also resulted in increase of sodium nitroprusside (SNP)-induced re-After incubation with Vit E, the vascular relaxation responses to ACh increased in an endothelium-dependent manner, when compared with the hypothermia-treated group.

CONCLUSIONThe vascular function of constriction was attenuated by hypothermia, while the relaxation was increased. Vit E could prevent the hypothermia-induced decrease in vascular endothelial cells.

Animals ; Arteries ; drug effects ; physiology ; Cold Temperature ; Hypothermia ; In Vitro Techniques ; Male ; Mice ; Prazosin ; pharmacology ; Solanaceous Alkaloids ; pharmacology ; Vasoconstriction ; drug effects ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology ; Vitamin E ; pharmacology

OBJECTIVETo investigate the antithrombotic effects and its molecular mechanisms of prazosin combined with anisodamine (Ani).

METHODSIsolated rat tail artery rings model was employed to evaluate the vasodilative effects of drugs, mice tail thrombosis model induced by carrageenan was used to study the antithrombotic effects and its molecular mechanisms of the drug composition.

RESULTSAmong alpha1-adrenoreceptor antagonists, prazosin(Pra) had the greatest relaxation rate, which was (82.6 +/- 8.9)%, and the EC50 value was 0.44 micromol/L. The drug composition of anisodamine and prazosin of different doses could decrease the length of the tail thrombosis from (24.6 +/- 4.6)mm to (6.9 +/- 2.7)mm, and the rate of thrombosis was decreased from 86.6% to 50.0%. The drug composition could prolong the prothrombin time (PT) distinctively, but it had no effect on the activated partial thromboplastin time (APTT). It also could restrain the decrease of serum levels of tissue plasminogen activator (t-PA) and 6- Keto -PGF1alpha as well as the increase of type-1 plasminogen activator inhibitor (PAI-1) and thromboxane B2 (TXB2) in the mice.

CONCLUSIONThe drug composition formed by anisodamine and prazosin has good effects of relaxing extremities tiny blood vessels and it can fight against thrombosis, its antithrombotic mechanisms may be related to the influence of the extrinsic coagulation pathway, inhibition of platelet activation functions and the promotion of fibrinolysis function.

Adrenergic alpha-1 Receptor Antagonists ; pharmacology ; Animals ; Disease Models, Animal ; In Vitro Techniques ; Male ; Prazosin ; pharmacology ; Rats ; Rats, Wistar ; Solanaceous Alkaloids ; pharmacology ; Thrombosis ; drug therapy

The purpose of this study is to investigate the penetration effects and mechanism of N-arginine chitosan (ACS). This novel transdermal enhancer with a mimetic structure of cell-penetration peptides was synthesized by introducing hydrophilic arginine groups to the amino-group on chitosan's side chain. The structure of ACS was confirmed by FT-IR, 1H NMR and element analysis. In addition, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was used to study the protein conformation and the water content of stratum corneum, and the result suggested that ACS can change the orderly arrangement of the molecules in the stratum corneum, making the stack structure of keratin become loose. And ACS can increase the water content of the stratum corneurn. Inverted fluorescence microscope and flow cytometry were used to examine penetration effect of ACS on Hacat cell. The result confirmed that the uptake of ACS was enhanced with increased substitution degree of arginine by 4-8 folds compared to chitosan. In vitro penetration studies on three electrical types of drugs were carried out using three model drugs of negatively charged aspirin, positively charged terazosin and neutral drug isosorbide mononitrate by the method of Franz diffusion cells. The results showed that ACS has obviously penetration of the negatively charged drug aspirin, and certain penetration of neutral drug issorbide mononitrate, but inhibition of positively charged terazosin. In vivo imaging technology research results show that the ACS can significantly enhance the fluorescence intensity of morin, which is the auto-fluorescence anionic drug. These obtained results suggested that ACS, as a promising transdermal enhancer, can change the structure of the keratinocytes and analog penetrating peptides promote absorption, but have certain selectivity for the drug.
Administration, Cutaneous ; Animals ; Arginine ; chemical synthesis ; chemistry ; pharmacology ; Aspirin ; administration & dosage ; pharmacokinetics ; Cell Line ; Cell Survival ; drug effects ; Cell-Penetrating Peptides ; chemical synthesis ; chemistry ; pharmacology ; Chitosan ; chemical synthesis ; chemistry ; pharmacology ; Drug Carriers ; Humans ; Isosorbide Dinitrate ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Keratinocytes ; cytology ; Male ; Mice ; Prazosin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Skin Absorption ; drug effects

OBJECTIVETo demonstrate the inhibitory effect of kappa-opioid receptor activation by U50488H on hypertrophy induced by NE in cultured neonatal rat cardiac myocytes and compare its effect with that of prazosin and propranolol.

METHODSThe cellular proliferation was determined with crystal violet staining. The protein content was assayed with Lowry's method. The cardiomyocytes volumes were measured by computer photograph analysis system. The protein synthesis was assayed with [3H]-lencine incorporation method.

RESULTS(1) NE significantly induced the increase of protein content, [3H]-leucine incorporation and cell size without a concomitant increase in cell number in low serum medium. OThese responses were partially suppressed by prazosin or propranolol alone and completely abolished by both in combination. U50488H significantly inhibited the NE-induced increase of protein content, [3H]-leucine incorporation and cell size. The inhibitory effects of U50488H on NE-induced cardiac hypertrophy were greater than either prazosin or propranolol, but comparable to combination of both.

CONCLUSIONNE, acting via both alpha1- and beta-adrenergic pathway, stimulates myocyte hypertrophy. Stimulating kappa-opioid receptor significantly inhibits NE-induced cardiac hypertrophy, which may be related with alpha1- and beta1-adrenergic pathway.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer ; pharmacology ; Adrenergic alpha-1 Receptor Antagonists ; pharmacology ; Adrenergic beta-Antagonists ; pharmacology ; Animals ; Animals, Newborn ; Cardiomegaly ; chemically induced ; pathology ; prevention & control ; Cell Enlargement ; drug effects ; Cells, Cultured ; Female ; Male ; Myocytes, Cardiac ; cytology ; Norepinephrine ; Prazosin ; pharmacology ; Propranolol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, kappa ; agonists

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 (0.1 micromol x L(-1)). The alpha1-adrenoceptor antagonist prazosin (1 micromol x L(-1)) did not affect the vascular responses to the electric field stimulation (2 -8 Hz). After a combination treatment with both alpha,beta-meATP (3 micromol x L(-1), desensitizing P2X1 receptors) and prazosin (1 micromol x L(-1)), the vasoconstrictive responses to electric field stimulation were abolished. When the arterial preparation was treated with ISMN (one preparation was exposed to only one concentration of ISMN), ISMN at 0.1 mmol x L(-1) significantly inhibited the vasoconstriction induced by electric stimulation at 8 Hz, 0.3 and 1.0 mmol x L(-1) significantly inhibited the vasoconstrictive responses to electric stimulation at 2 - 16 Hz. The highest concentration of ISMN (1.0 mmol x L(-1)) reduced the vasoconstrictive responses by 46% (2 Hz), 47% (4 Hz), 34% (8 Hz) and 22% (16 Hz), separately. ISMN (0.3 and 1.0 mmol x L(-1)) did not affect the vascular responses to exogenous noradrenaline (0.01-100 micromol x L(-1)) and adenosine triphosphate (1 mmol x L(-1)). It is reasonable to suggest that ISMN inhibits the purinergic vasoconstriction induced by sympathetic nerve stimulation via a prejunctional mechanism.
Adenosine Triphosphate ; analogs & derivatives ; pharmacology ; Adrenergic alpha-Antagonists ; pharmacology ; Animals ; Arteries ; drug effects ; Delayed-Action Preparations ; Electric Stimulation ; Isosorbide Dinitrate ; administration & dosage ; analogs & derivatives ; pharmacology ; Male ; Norepinephrine ; pharmacology ; Prazosin ; pharmacology ; Purinergic P2 Receptor Agonists ; Rabbits ; Receptors, Purinergic P2X ; Vasoconstriction ; drug effects

OBJECTIVE: To investigate the effects of prazosin on the proliferation and apoptosis of human leukemia cell line (K562). METHODS: The effects of prazosin on the proliferation of K562 cells were evaluated by liquid culture assay, MTT assay and colony formation assay. Prazosin induced K562 cells toward apoptosis and this was verified by cellular morphology, Hoechst33258 fluorescence staining and flow cytometry respectively. RESULTS: The proliferation of K562 leukemia cells was inhibited by prazosin in a dose-dependent manner. With prazosin (5 x 10(-6) mol/L), the apoptosis cells could be observed morphologically, or by Hoechst 33258 fluorescence staining and flow cytometry. CONCLUSION Prazosin can inhibit the proliferation of K562 cells and induce the apoptosis of K562 cells.
Adrenergic alpha-Antagonists ; pharmacology ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Flow Cytometry ; Humans ; K562 Cells ; Prazosin ; pharmacology

OBJECTIVEThe aim of the present study is to compare the effects of two alpha1-adrenoceptor antagonist terazosin and alfuzosin together with one alpha-adrenoceptor antagonist phenoxybenzamine on androgen-independent prostate cancer cell lines PC-3 and DU145.

METHODSTwo androgen- independent cell lines, PC-3 and DU145, were used to determine the cell viability, colony-forming ability as well as cell cycle characteristics after exposure to these three drugs.

RESULTSThis study showed that terazosin inhibited not only prostate cancer cell growth but also colony-forming ability, which is the main target of clinical treatment. On the other hand, alfuzosin and phenoxybenzamine have no effect on cell viability and colony forming ability of PC-3 and DU145. In addition, the terazosin inhibits cell growth through G(1) phase cell cycle arrest.

CONCLUSIONThis study provided the evidence that alpha1-adrenoceptor antagonist terazosin may have a therapeutic potential in the treatment of advanced androgen-independent prostate cancer.

Adrenergic alpha-Antagonists ; pharmacology ; Antineoplastic Agents ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Humans ; Male ; Phenoxybenzamine ; pharmacology ; Prazosin ; administration & dosage ; analogs & derivatives ; pharmacology ; Prostatic Neoplasms ; pathology ; Quinazolines ; pharmacology

OBJECTIVETo study the effect of nitric oxide donor and alpha(1)-receptor antagonist on proliferation/apoptosis of hyperplastic prostatic stromal cells in vitro.

METHODSPrimary cultured prostatic stromal cells were treated by nitric oxide donor SNP and Terazosin, and the antiproliferative index and apoptosis index were determined by MTT assay and TUNEL respectively.

RESULTSThere was a significant dose-effect relationship between SNP and the antiproliferative effects, while Terazosin showed no antiproliferative effects and the combination of SNP and Terazosin showed no strengthen effects. Terazosin significantly induced apoptosis, but SNP showed no effect on induction of apoptosis, while there were much more effects of inducing apoptosis in the combination of Terazosin and SNP than the Terazosin alone.

CONCLUSIONSTerazosin induces apoptosis in cultured BPH stromal SMCs with little effect on the cell proliferation. SNP inhibits the proliferation of the cells without affecting apoptosis. The apoptosis induction effect is enhanced when Terazosin is combined with SNP, but they do not have an additive antiproliferative effect.

Adrenergic alpha-Antagonists ; pharmacology ; Apoptosis ; drug effects ; Dose-Response Relationship, Drug ; Drug Synergism ; Humans ; In Situ Nick-End Labeling ; Male ; Nitric Oxide Donors ; pharmacology ; Prazosin ; analogs & derivatives ; pharmacology ; Prostatic Hyperplasia ; drug therapy ; pathology ; Stromal Cells ; drug effects ; pathology

AIMTo observe the role of melatonin receptor and GABAA receptor in sleeping time prolonged by melatonin in mice.

METHODSThe absence of the righting reflex was considered as the sleep onset and the duration of the loss of the righting reflex was recorded as the sleeping time. The effects of receptor agonist and antagonist on hypnotic activity of melatonin were studied in the paper.

RESULTSPrazosin hydrochloride, the blocker of melatonin 3 receptor, didn't affect the sleeping time prolonged by melatonin in mice. GABA, the endogenous agonist of GABA receptor, significantly potentiated the hypnotic activity of melatonin. When picrotoxin, the ligand of picrotoxin site on GABAA receptor, used together with melatonin, it significantly antagonized the sleeping time prolonged by melatonin, however, bicuculline, the specific antagonist of GABA binding site in GABAA receptor, didn't affect the hypnotic activity of melatonin in mice.

CONCLUSIONMelatonin does not exhibit its potentiation sleeping time in mice through melatonin 3 receptor. Hypnotic activity of melatonin may be mediated through picrotoxin site on GABAA receptor.

Animals ; Bicuculline ; pharmacology ; Male ; Melatonin ; physiology ; Mice ; Mice, Inbred Strains ; Picrotoxin ; pharmacology ; Prazosin ; pharmacology ; Receptors, GABA-A ; physiology ; Receptors, Melatonin ; physiology ; Sleep ; physiology