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 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

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

OBJECTIVETo study the effects of an alpha(1)-adrenoceptor antagonist, terazosin on the androgen-independent prostate cancer cell lines PC-3 and DU145.

METHODSTwo androgen independent cell lines, PC-3 and DU145, were used to determine cell viability, colony-forming ability, as well as cell cycle distribution, after exposure to terazosin. Western blot analysis was used to determine the expression of p21WAF1 and p27KIP1.

RESULTSThis study shows that terazosin inhibits not only prostate cancer cell growth but also its colony forming ability, both of which are main targets of clinical treatment. In addition, terazosin is shown to inhibit cell growth through G1 phase cell cycle arrest and the up-regulation of p27(KIP1).

CONCLUSIONThis study provides evidence that the alpha(1)-adrenoceptor antagonist terazosin may have therapeutic potential in the treatment of advanced hormone refractory prostate cancer.

Adrenergic alpha-Antagonists ; pharmacology ; Antineoplastic Agents ; pharmacology ; Cell Division ; drug effects ; Cell Line ; Humans ; Male ; Prazosin ; analogs & derivatives ; pharmacology ; Prostatic Neoplasms ; pathology ; Tumor Cells, Cultured

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

We investigated the effect of alpha-adrenergic and cholinergic receptor agonists on Ca2+ current in adult rat trigeminal ganglion neurons using whole-cell patch clamp methods. The application of acetylcholine, carbachol, and oxotremorine (50 muM each) produced a rapid and reversible reduction of the Ca2+ current by 17+/-6%, 19+/-3% and 18+/-4%, respectively. Atropine, a muscarinic antagonist, blocked carbachol-induced Ca2+ current inhibition to 3 +/- 1%. Norepinephrine (50 muM) reduced Ca2+ current by 18 +/- 2%, while clonidine (50 muM), an alpha2-adrenergic receptor agonist, inhibited Ca2+ current by only 4 +/- 1%. Yohimbine, an alpha2-adrenergic receptor antagonist, did not block the inhibitory effect of norepinephrine on Ca2+ current, whereas prazosin, an alpha1-adrenergic receptor antagonist, attenuated the inhibitory effect of norepinephrine on Ca2+ current to 6 +/- 1%. This pharmacology contrasts with alpha2-adrenergic receptor modulation of Ca2+ channels in rat sympathetic neurons, which is sensitive to clonidine and blocked by yohimbine. Our data suggest that the modulation of voltage dependent Ca2+ channel by norepinephrine is mediated via an alpha1-adrenergic receptor. Pretreatment with pertussis toxin (250 ng/ml) for 16 h greatly reduced norepinephrine- and carbachol-induced Ca2+ current inhibition from 17 +/- 3% and 18 +/- 3% to 2 +/- 1% and 2 +/- 1%, respectively. These results demonstrate that norepinephrine, through an alpha1-adrenergic receptor, and carbachol, through a muscarinic receptor, inhibit Ca2+ currents in adult rat trigeminal ganglion neurons via pertussis toxin sensitive GTP-binding proteins.
Acetylcholine ; Adult ; Animals ; Atropine ; Carbachol ; Clonidine ; GTP-Binding Proteins ; Humans ; Neurons ; Norepinephrine ; Oxotremorine ; Pertussis Toxin ; Pharmacology ; Prazosin ; Rats ; Receptors, Muscarinic ; Trigeminal Ganglion ; Yohimbine

Alpha1a-adrenergic receptor (AR) primarily mediates the contraction of the prostatic and cavernous smooth muscles. Among clinically available alpha1-AR antagonists for the medical management of benign prostatic hyperplasia (BPH), tamsulosin has a modest selectivity for alpha1A- and alpha1D- over alpha1B-ARs. To compare the effects of various alpha1-AR antagonists on relaxation responses of cavernous and trigonal smooth muscles, isometric tension studies with relatively selective (tamsulosin) and non-selective (prazosin, doxazosin, and terazosin) alpha1A-AR antagonists, were conducted in the cavernous and trigonal muscle strips of rabbits (n=10 each). Tamsulosin had the strongest inhibitory effect on contraction of trigonal smooth muscle among the various alpha1-AR antagonists, and the inhibitory activities of prazosin, doxazosin, and terazosin were not statistically different. All alpha1-AR antagonists caused concentration-dependent relaxation of the cavernous muscle strips. Tamsulosin was shown to have greater potency than prazosin (more than 100-fold), doxazosin (more than 1000-fold), and terazosin (more than 1000-fold), in relaxation of cavernous smooth muscle. In conclusion, tamsulosin might be the most effective drug among the four commonly used alpha1-AR antagonists for the medical management of BPH. Tamsulosin might be a potential substitute for phentolamine in combination with vasoactive agents as an intracavernous injection therapy for patients with erectile dysfunction.
Adrenergic alpha-Antagonists/pharmacology* ; Animal ; Comparative Study ; Doxazosin/pharmacology* ; In Vitro ; Muscle Contraction/drug effects ; Muscle Relaxation/drug effects* ; Muscle, Smooth/physiology ; Muscle, Smooth/drug effects* ; Prazosin/pharmacology* ; Rabbits ; Receptors, Adrenergic, alpha-1/antagonists & inhibitors* ; Sulfonamides/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 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