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Transient growth signals which can be related to protein synthesis and cellular growth are of particular interest in the heart because of the incidence of cardiac hypertrophy in man. The isolated coronary perfused adult rat heart or the so-called Langendorff preparation, is an useful model in exploring not only protein synthesis but also c-fos/c-myc protooncogene and Heat Shock Protein (HSP) gene expression. Phenylephrine infusion in this preparation induces c-fos expression whether the heart is beating or reversibly or irreversibly arrested by solutions enriched in KCl. Norepinephrine has the same effect. Quantitative analysis with slot blots shows that in both cases the adrenergic effect has a dual origin since it is inhibited both by propranolol, a beta-adrenergic antagonist, and terazosine, a soluble alpha 1-adrenergic antagonist. We conclude that the isolated heart is a useful tool to explore the early changes in gene expression which occur in this tissue in response to various physiological stimuli.
These results demonstrate that daily treatment with an α-adrenergic receptor blocker induces capillary growth in human skeletal muscle, likely due to increased shear stress. The increase in capillarisation resulted in an increased fractional O2 extraction, a lower blood flow and venous lactate levels in the exercising leg. The increase in capillarisation, and concomitant functional readouts in the exercising leg, may provide a basis for novel angiotherapy. This article is protected by copyright. All rights reserved.
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These data suggest that prazosin exhibits anti-angiogenic activity and differentially modulates apoptotic pathways depending on the cell type.
One hundred patients were enrolled in the study. They were randomized into two groups (each group consisted of 50 patients). Terazosine and placebo were administered to the patients in Group 1 and terazosine plus propiverine HCL was administered to Group 2. The patients were evaluated by international prostate symptom score (IPSS), the first four questions of IPSS (IPSS4), the 8th question of IPSS (quality of life-QoL), overactive bladder symptom score questionnaire (OAB-q V8), PSA test, urodynamic studies, post voiding residue (PVR). All patients were followed for one year and were reassessed for comparison.
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A sensitive and simple detection method coupling ultra-performance liquid chromatography with tandem mass spectrometry was developed and validated to analyze sumatriptan levels in human plasma. The plasma sample preparations for the analysis were based on liquid-liquid extraction with ethyl acetate, evaporation, and reconstitution. MS/MS detection was performed on a triple-quadrupole tandem mass spectrometer by monitoring the protonated parent→daughter ion pairs at m/z 296→58 and m/z 388→71 for sumatriptan and terazosin (internal standard), respectively. The method was validated with respect to its specificity, linearity, sensitivity, accuracy, precision, recovery, and stability. The calibration curve was linear from 0.5 to 50 ng/mL (r>0.999). The mean extraction recovery for sumatriptan was higher than 62.3%. The method accuracy was within 97.4%, and the relative standard deviation of the intra- and inter-day precision values was within 11.7% at all quality control levels. Plasma samples that contained sumatriptan were stable under three freeze-thaw cycles, short- and long-term storage, and autosampler conditions. This method was successfully applied to a pharmacokinetic study conducted with 10 healthy volunteers. After oral administration of 50-mg sumatriptan and serial blood sampling over 12 h, the mean area under the plasma concentration-time curve from time 0 to 12 h and the maximum plasma concentration were 116.2 ng h/mL and 33.2 ng/mL, respectively.
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The treatment of benign prostate hyperplasia (BPH) presents 2 options: medical or surgical, and there are doubts about what is the best treatment since 80% of patients who undergo surgery become asymptomatic and 10 to 40% of those under medical regimen undergo surgery within a 5 years period. It is difficult to assess the actual costs of treating BPH in Brazil due to several factors, among them regional particularities and the scarcity of current statistical data.
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All articles in English identified from data sources were reviewed for relevance and uniqueness prior to inclusion.
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Benign prostatic hyperplasia (BPH) is very common in older men, causing symptoms that can markedly impair quality of life. Surgical treatment, typically transurethral resection of the prostate (TURP), is highly effective but can be costly and is associated with the risk for significant morbidity. Medical treatments for BPH are targeted toward reducing bladder outlet obstruction either by androgen blockade to reduce prostatic volume or alpha-adrenergic blockade to relax the smooth muscle tone of the prostate. In recent years, understanding of the sympathetic innervation of the prostate has improved. This has been paralleled by the development of alpha-adrenergic blocking agents, from nonselective alpha-antagonists, to selective alpha1-antagonists, to the more selective alpha1A-antagonists. It is anticipated that more specific agents will optimize the therapeutic effectiveness of alpha-adrenergic blockade in the prostate while reducing the side effects associated with alpha-adrenergic blockade in other areas of the body, such as the vascular system. This article reviews the evolution of alpha-blockade therapy in management of BPH, focusing on tamsulosin, an agent targeted toward the alpha1A-adrenoceptor that predominates in the prostate. Clinical trials in Europe and the United States have provided evidence that tamsulosin is effective at doses of 0.4 and 0.8 mg/day. At both doses, tamsulosin is associated with significant improvements in the American Urological Association symptom score and the mean and peak urinary flow rates as compared with placebo. This once-daily alpha1A-adrenergic antagonist is well-tolerated, with a minimal potential for the side effects associated with alphas-blocker therapy.
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To assess the reversibility of left ventricular hypertrophy (LVH) during terazosin therapy, we studied changes in LVH as determined by echocardiography and humoral parameters before and after three and 12 months of terazosin monotherapy in ten patients. Blood pressure decreased within four weeks of treatment and the antihypertensive effect was sustained throughout 12 months. Left ventricular mass index decreased significantly from 126 +/- 22 g/m2 to 109 +/- 24 g/m2 and 98 +/- 23 g/m2 after 3 and 12 months respectively. Interventricular septum (11.2 to 9.8 and 9.0 mm) and posterior wall thickness (10.4 to 9.6 and 8.8 mm) also decreased significantly, whereas left ventricular internal dimensions were unchanged. Total peripheral resistance decreased significantly after initiation of treatment, but cardiac output did not change. Plasma volume, plasma renin activity and plasma noradrenaltine levels were unchanged by terazosin. Thus, terazosin monotherapy reversed LVH associated with decreased peripheral resistance. It is suggested that the reversal of LVH by terazosin is mainly due to the reduction in ventricular afterload and that humoral factors are not involved in its mechanism.
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To investigate the effects of alpha receptor blockers used in the treatment of benign prostatic hyperplasia (BPH) on endothelial functions, coagulation parameters, and arterial blood pressure.
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The effects of different alpha-1 adrenoceptor blockers on the urethra and the cardiovascular system were evaluated using an in vivo isovolumetric intra-urethral pressure model in New Zealand white rabbits. The urethra of anesthetized male rabbits was cannulated through the bladder and secured at the vesico-urethral junction. The distal side of urethra under the pubic bone was also closed to allow measurement of the intra-urethral pressure. Both the intra-urethral pressure and the femoral arterial pressure were monitored. The effects of five different alpha-1 adrenoceptor blockers on the increases in both the intra-urethral pressure and blood pressure induced by phenylephrine were then examined. The inhibition rate of the alpha-1 adrenoceptor blockers prazosin, bunazosin, terazosin, alfuzosin and tamsulosin on the increase in intra-urethral pressure caused as a result of contraction by phenylephrine was 87.5 +/- 4.5% (mean +/- S.E.), 88.0 +/- 7.2%, 86.2 +/- 6.2%, 81.4 +/- 4.8% and 92.5 +/- 5.0% respectively. The potency ranking of these alpha-1 adrenoceptor blockers was tamsulosin > bunazosin > prazosin > terazosin > alfuzosin. Their inhibition rate of the arterial pressure increase induced by phenylephrine was 81.9 +/- 5.0%, 86.2 +/- 5.9%, 76.0 +/- 6.0%, 63.6 +/- 5.7% and 58.0 +/- 5.2% respectively, with a potency ranking of bunazosin > prazosin > terazosin > alfuzosin > tamsulosin. We therefore conclude that the alpha-1 adrenoceptor blockers bunazosin and prazosin have a more potent action on both the urethra and the vascular system. However, tamsulosin and alfuzosin displayed a marked blockade of the increased urethral pressure induced by phenylephrine, with much less of a blockade of arterial pressure. In the present study, tamsulosin has been shown to be the most sensitive and powerful of the alpha-1 adrenoceptor blockers on urethral smooth muscle.
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To evaluate the efficacy and safety of Compound Xuanju Capsule (CXC) in the treatment of chronic prostatitis with erectile dysfunction (ED).
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For the entire group, IPSS decreased from 13.25 +/- 3.39 to 7.38 +/- 3.21 (44.6%), Qmax increased from 9.75 +/- 1.95 to 11.00 +/- 3.23 ml/s (21%), Pmax decreased from 109.75 +/- 35.72 to 93.88 +/- 20.91 cm. H2O (14.4%), Pdet decreased from 84.00 +/- 23.71 to 74.00 +/- 15.53 cm. H2O (16.8%), DCD increased from 127.63 +/- 53.99 to 130.13 +/- 45.41s (2.7%). There was a weak correlation between either Pmax or Pdet and therapeutic response (defined as a IPSS decrease of 40% and an increase in Qmax of 30%). There was a significant correlation with therapeutic response of DCD > 60 s (p < 0.05, r = 0.56).
alpha 1-adrenoceptor antagonists (blockers) are now commonly used in the treatment of the symptoms of lower urinary tract obstruction. Originally phenoxybenzamine, a non-selective antagonist at both alpha 1- and alpha 2-adrenoceptors, was used by Marco Caine. In an attempt to minimize side effects, selective alpha 1-antagonists, e.g. prazosin, were subsequently developed. More recently, agents such as alfuzosin, doxazosin, terazosin, and tamsulosin have been introduced and claims of "uroselectivity" and "prostate" selectivity have emerged.
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Doxazosin is a long-acting alpha 1-adrenoceptor antagonist structurally related to prazosin and terazosin. Its antihypertensive effect is produced by a reduction in the smooth muscle tone of peripheral vascular beds resulting in a decrease in total peripheral resistance without significant effect on cardiac output or heart rate. In benign prostatic hyperplasia, doxazosin's effect of relieving bladder outflow obstruction is produced through a reduction in prostatic tone mediated via alpha 1-adrenoceptor blockade. In most comparative trials doxazosin has proven to be equally effective as the comparator drug in the treatment of mild to moderate hypertension. It has been used in a variety of patient populations including the elderly, Blacks, smokers, and patients with concomitant disease states such as renal dysfunction, hypercholesterolaemia, non-insulin dependent diabetes mellitus (NIDDM) and respiratory disease. Doxazosin has also been used successfully in combination with beta-adrenoceptor antagonists, diuretics, calcium channel antagonists, and angiotensin-converting enzyme inhibitors in patients with hypertension that is uncontrolled with monotherapy. Doxazosin has a beneficial effect on some of the risk factors associated with coronary heart disease including elevated serum lipid levels, impaired glucose metabolism, insulin resistance and left ventricular hypertrophy. Modest decreases in total cholesterol, low density lipoprotein cholesterol and triglycerides are seen with doxazosin therapy while small increases in high density lipoprotein cholesterol and the high density lipoprotein cholesterol/total cholesterol ratio are consistently reported. Some studies have reported an improvement in glucose tolerance although this effect has been more consistently seen in nondiabetic patients than in patients with NIDDM. Additionally, doxazosin produces a similar reduction in left ventricular hypertrophy to other antihypertensive agents. Modelling-based calculations suggest that doxazosin significantly reduces the risk of developing coronary heart disease in patients with mild to moderate hypertension, although this remains to be confirmed in long term prospective studies. Doxazosin appears to be a promising agent in the treatment of urinary symptoms associated with benign prostatic hyperplasia. Similar to other alpha 1-adrenoceptor antagonists, doxazosin treatment produces increases in peak and mean urinary flow rates and improves other objective and symptomatic measures.(ABSTRACT TRUNCATED AT 400 WORDS)
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A total of 15 clinical studies were identified and evaluated. Many studies showed an improvement in female lower-urinary-tract symptoms and dysfunction using α-adrenergic blockers. Most studies also reported adverse drug events of α-adrenergic blockers such as dizziness and hypotension. However, limitations of the studies conducted to date include small sample sizes, inconsistent study designs, and short duration of therapy.
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Communication between neuronal and glial cells is thought to be very important for many brain functions. Acting via release of gliotransmitters, astrocytes can modulate synaptic strength. The mechanisms underlying gliotransmission remain uncertain with exocytosis being the most intriguing and debated pathway. We demonstrate that astroglial α1-adrenoreceptors are very sensitive to noradrenaline (NA) and make a significant contribution to intracellular Ca(2+)-signaling in layer 2/3 neocortical astrocytes. We also show that astroglial α1-adrenoreceptors are prone to desensitization upon prolonged exposure to NA. We show that within neocortical slices, α-1adrenoreceptors can activate vesicular release of ATP and D-serine from cortical astrocytes which initiate a burst of ATP receptor-mediated currents in adjacent pyramidal neurons. These purinergic currents can be inhibited by intracellular perfusion of astrocytes with Tetanus Toxin light chain, verifying their origin via astroglial exocytosis. We show that α1 adrenoreceptor-activated release of gliotransmitters is important for the induction of synaptic plasticity in the neocortex:long-term potentiation (LTP) of neocortical excitatory synaptic potentials can be abolished by the selective α1-adrenoreceptor antagonist terazosin. We show that weak sub-threshold theta-burst stimulation (TBS) can induce LTP when astrocytes are additionally activated by 1 μM NA. This facilitation is dependent on the activation of neuronal ATP receptors and is abolished in neocortical slices from dn-SNARE mice which have impaired glial exocytosis. Importantly, facilitation of LTP by NA can be significantly reduced by perfusion of individual astrocytes with Tetanus Toxin. Our results strongly support the physiological importance of astroglial adrenergic signaling and exocytosis of gliotransmitters for modulation of synaptic transmission and plasticity.
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To investigate the regulatory effects of total ginsenosides and the conventional antihypertensive agents (captopril, amlodipine, terazosin and hydrochlorothiazide) on the blood pressure and perturbed metabolism in spontaneously hypertensive rats (SHRs) and to analyze the cause-effect relationships between high blood pressure and the metabolic disorders of hypertension.
In this review, the relationship between hypertension and abnormal carbohydrate metabolism is explored. A review of the current literature reveals that people with hypertension are also likely to suffer from insulin resistance, glucose intolerance, and hyperinsulinemia. Likewise, hypertension is prevalent in obese and diabetic patients. Deficiency of insulin at the cellular level may be a common mechanism in the development of hypertension in patients with type I or type II diabetes mellitus. Essential hypertension appears to be an insulin-resistant state. Insulin resistance may engender hypertension by increasing peripheral vascular resistance as well as by increasing salt retention at the level of the kidney. Therefore effective antihypertensive therapy should include agents that do not adversely affect carbohydrate metabolic abnormalities. Commonly used antihypertensive agents, such as thiazide, thiazide-like diuretics, and beta-blockers, are associated with glucose intolerance and increased insulin resistance. In contrast, angiotensin-converting enzyme inhibitors, calcium antagonists, and peripheral alpha-blockers (such as prazosin and terazosin) do not adversely affect glucose tolerance or insulin sensitivity. In addition, alpha-blockers have a positive effect on the serum lipid profile. The entire multifactorial cardiac risk profile must be considered when choosing therapeutic agents for conditions that have an impact on cardiovascular disease.
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Terazosin is a selective alpha1-adrenoceptor antagonist. A double-blind, randomized, placebo-controlled, two-period study evaluated the effects of posture and of oral and intravenous administration of terazosin on blood pressure and heart rate in patients with hypertension. At least one week after withdrawal of all antihypertensive medications, 31 patients with sitting diastolic blood pressure of 95 to 114 mmHg were enrolled in the study. After a 24-hour, single-blind, placebo lead-in phase, the patients were randomized to receive either oral terazosin (1 mg on day 1, 2 mg on day 2, and 5 mg on days 3 and 4), a 12-hour intravenous infusion of terazosin (2.5 mg, 5 mg, or 7.5 mg), or placebo for 4 consecutive days. Head-up tilt (60 degrees for 20 minutes) evaluations were performed before and 0.5, 1.5, 2.5, 6, 12, and 16 hours after start of administration during the placebo lead-in phase and on each of the 4 days of the double-blind treatment phase. Blood pressure and heart rate were monitored every 2 minutes during the 20-minute tilt. Statistically significantly larger mean changes in blood pressure and heart rate were observed with the 7.5-mg intravenous dose of terazosin compared with those after oral terazosin or placebo. With respect to intravenous terazosin, the orthostatic changes were maximal on the first day of the 4-day treatment and increased with increasing doses of terazosin. Maximum orthostatic changes in blood pressure after oral administration of terazosin were not significantly different from those observed with placebo. The most common treatment-emergent adverse events during tilt were dizziness and nausea. Dizziness occurred more frequently with intravenous terazosin than with oral terazosin. The results of this study indicate that oral dose titration of terazosin rather than a slower rate of terazosin infusion minimized the postural effects on blood pressure and associated symptoms during head-up tilt.
Study, patient characteristics and outcomes data were extracted in duplicate onto standardized forms utilizing a prospectively developed protocol. The main outcome measure for comparing the effectiveness of terazosin with placebo or other BPO medications was change in urological symptoms as measured by validated symptom scores. Secondary outcomes included urodynamic measures. The main outcome measure for adverse effects was the number of men reporting side effects. We also evaluated the number of men withdrawing from treatment and the number withdrawing due to adverse effects.
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The purpose of this study was to evaluate the effects of the alpha 1-blocking agent terazosin on blood pressure (BP) and blood lipids in a large, variant population of patients with hypertension. A total of 16,917 patients with hypertension were evaluated at 2214 primary and community care facilities; 7808 of these patients had not been treated previously for hypertension; 3928 were switched to terazosin from another antihypertensive agent; and 5181 received terazosin in addition to an agent that had not controlled their hypertension. Terazosin produced highly significant reductions in systolic (-18.2 +/- 0.2 mm Hg) and diastolic (-13.2 +/- 0.1 mm Hg) BP when used as monotherapy (mean dose, 3.1 mg; range, 2 to 10 mg) without causing a significant increase in heart rate. Equal antihypertensive efficacy was demonstrated in men, women, blacks, and whites of all ages, with particular benefit to elderly patients (> or = 65 years of age) with systolic hypertension. Comparative studies indicated that terazosin had equal antihypertensive efficacy in combination with diuretics, beta-blockers, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors. Patients who had not responded to monotherapy with one of these classes of antihypertensive drugs showed significant reductions of BP after terazosin, in the following average doses, was added to diuretics, 3.1 mg; beta-blockers, 3.4 mg; calcium channel blockers, 3.3 mg; and ACE inhibitors, 3.4 mg. Terazosin produced highly significant reductions in blood levels of total cholesterol (-5.0%), triglycerides (-6.1%), and low-density lipoprotein cholesterol (-7.6%) without change in high-density lipoprotein cholesterol when used as monotherapy. Similar favorable effects on blood lipid levels were demonstrated when terazosin was used in combination with all other classes of antihypertensive drugs. The greatest reductions in blood cholesterol (-9.2%) were observed among patients with hyperlipidemia (total cholesterol > or = 240 mg/dL). Terazosin maintained its antihypertensive efficacy and was well tolerated by patients with a variety of concomitant diseases, including congestive heart failure, peripheral vascular disease, chronic obstructive pulmonary disease, benign prostatic hyperplasia, diabetes, and obesity. Adverse effects occurred in 17.9% of patients and caused 2.2% to drop out of the study. The most frequent adverse effects were dizziness (4.8%), headache (2.5%), and asthenia (2.4%). Only 0.4% suffered syncope and 0.2% impotence. These data demonstrate the usefulness of terazosin as monotherapy or add-on therapy for treatment of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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After considering the clinical and physiopathological aspects of Raynaud's phenomenon, the authors have evaluated the medium effects of therazosine in 2 groups of patients, respectively with idiopathic and secondary Raynaud's phenomenon. The results show that the therazosin determines a decrease of number, intensity and duration of vasospastic attacks to the hands as well as an improvement of telethermographic and ultrasonographic findings.
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Our objective was to determine the effectiveness of alpha1-blockers on upper tract stasis in men with spinal cord injury (SCI) who use reflex voiding for bladder management.
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Benign prostatic hyperplasia (BPH) is one of the most common medical conditions in older men in the United States. BPH is often associated with a reduction in quality of life and may progress to acute urinary retention (AUR), the inability to pass any urine. Recently, a 4-year placebo-controlled clinical trial known as the Proscar Long-Term Efficacy and Safety Study (PLESS) demonstrated that finasteride use reduces the risk of developing AUR by 57% and the need for BPH-related surgery by 55%. The economic implications of these findings were investigated using a model-based decision-analytic approach to compare finasteride with both watchful waiting and alpha-blocker therapy. The modeling used the longest-term published controlled data concerning alpha-blockers, which were for the alpha-blocker terazosin. The base case considered a 64-year-old man (the mean age of a PLESS patient) with prostatic enlargement on digital rectal examination and moderate-to-severe symptoms of BPH. The model suggested savings in surgical and AUR costs with finasteride versus watchful waiting, with an estimated 25% of total finasteride costs recouped in savings on surgical events avoided in the first year. Over 2 years, the expected cost per patient starting finasteride therapy was $2304, whereas the expected cost per patient starting terazosin was $2334. Analyses also explored the variation in economic results by baseline levels of prostate-specific antigen (PSA), a proxy for prostate volume. For patients with PSA levels > or =1.4 ng/mL, expected 2-year costs with finasteride and terazosin were $2342 and $2479, respectively. For patients with PSA levels > or =3.3 ng/mL, expected 2-year costs with finasteride were $373 less than with terazosin ($2347 vs $2720). Results were robust over a range of model assumptions and cost estimates. The analyses illustrate that all medical interventions, including watchful waiting, have associated costs. Finasteride shows cost offsets compared with watchful waiting and cost savings compared with terazosin over 2 years. Finasteride appears to be more economical in men with higher PSA levels.
alpha1-Receptor-antagonist therapy improved upper tract stasis in men with SCI. The urodynamic parameter that changed in those with resolution of upper tract stasis was the duration of uninhibited contractions, which decreased significantly.
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Terazosin treatment did not affect the weight of the ventral prostate gland. The prostate contains hyaluronic acid, chondroitin sulfate (CS), dermatan sulfate (DS), and heparan sulfate (HS), MMP-2, TIMP-1, and TIMP-2, but not MMP-9. Terazosin caused a significant increase in the relative content of DS and a significant decrease in the relative content of CS and to a lesser extent of HS. Terazosin evoked a significant increase in the activity of proMMP-2 and MMP-2 but did not affect TIMP.