Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The control of high blood pressure (BP) after awakening in the morning (morning hypertension) as determined by home BP (HBP), as well as BP control throughout the day, may prevent diabetic vascular complications. We examined the effect of an alpha-adrenergic blocker (doxazosin) on BP measurements taken by HBP after awakening and during clinic visits (CBP) in 50 patients with type-2 diabetes and morning hypertension. We evaluated the urinary albumin excretion rate as an indicator of nephropathy. Doxazosin was taken orally once at bedtime for 1 to 3 months. The mean (+/- SD) dose was 2.9 +/- 2.1 mg/day (1 to 8 mg/day). The BP was measured monthly at the clinic during the day and at home after awakening in the morning. In this short-term trial (2.8 +/- 0.4 months), the systolic HBP decreased significantly from 164 +/- 17 mmHg before treatment to 146 +/- 19 mmHg after treatment, and the diastolic HBP decreased significantly from 85 +/- 14 mmHg before treatment to 80 +/- 9 mmHg after treatment. The systolic, but not the diastolic CBP, decreased significantly after treatment. There was no significant difference in the systolic or diastolic values between the HBP and the CBP after treatment. The percentage change in the systolic HBP after treatment was three times greater than for the systolic CBP. The median (interquartile) urinary albumin excretion rate decreased significantly (P < 0.001) from 62 (25-203) mg/g creatinine before treatment to 19 (9-76) mg/g creatinine after treatment. On multiple regression analysis, the decrease in the systolic HBP with treatment positively correlated with the reduction in urinary excretion of albumin. The control of morning hypertension reduced the albuminuria found in both untreated and treated hypertensive patients with type-2 diabetes. Bedtime administration of doxazosin appears to be safe and effective in reducing morning hypertension as measured by HBP. This finding also demonstrates that HBP taken in the morning has a stronger predictive power for the albuminuria level than does CBP.
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PMID:The bedtime administration of doxazosin controls morning hypertension and albuminuria in patients with type-2 diabetes: evaluation using home-based blood pressure measurements. 1592 Oct 73

Pituitary tumors are common and cause considerable morbidity due to local invasion and altered hormone secretion. Doxazosin (dox), a selective alpha(1)-adrenergic receptor antagonist, used to treat hypertension, also inhibits prostate cancer cell proliferation. We examined the effects of dox on murine and human pituitary tumor cell proliferation in vitro and in vivo. dox treatment inhibited proliferation of murine pituitary tumor cells, induced G(0)-G(1) cell cycle arrest, and reduced phosphorylated retinoblastoma levels. In addition, increased annexin-fluorescein isothiocyanate immunoreactivity and cleaved caspase-3 levels, in keeping with dox-mediated apoptosis, were observed in the human and murine pituitary tumor cells, and dox administration to mice, harboring corticotroph tumors, decreased tumor growth and reduced plasma ACTH levels. dox-mediated antiproliferative and proapoptotic actions were not confined to alpha-adrenergic receptor-expressing pituitary tumor cells and were unaffected by cotreatment with the alpha-adrenergic receptor blocker, phenoxybenzamine. dox treatment led to reduced phosphorylated inhibitory kappaB (IkappaB)-alpha expression, and nuclear factor-kappaB transcription and decreased basal and TNFalpha-induced proopiomelanocortin transcriptional activation. These results demonstrate that the selective alpha(1)-adrenergic receptor antagonist dox inhibits pituitary tumor cell growth in vitro and in vivo by mechanisms that are in part independent of its alpha-adrenergic receptor-blocking actions and involve down-regulation of nuclear factor-kappaB signaling. dox is proposed as a possible novel medical therapy for pituitary tumors.
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PMID:Alpha1-adrenergic receptor antagonists: novel therapy for pituitary adenomas. 1602 Apr 84

The role of oxidative stress in the pathophysiology of hypertension has stimulated the investigation of strategies to reduce oxidative stress via antioxidant defenses. Using a molecular biology approach, we report, in essential hypertensive patients, the effect of doxazosin treatment on the mononuclear cell gene and protein expression of two major elements in the oxidative stress and vascular remodeling-related pathways: p22(phox) and PAI-1. Ten essential hypertensive patients were treated with Doxazosin (4 mg/day) for two weeks (EH + D) and compared with ten untreated hypertensive patients (EH) and ten normotensive subjects (C). In EH p22(phox) and PAI-1 mRNA and protein level was increased compared with C. In EH + D, doxazosin reduced p22(phox) and PAI-1 gene and protein expression, which was similar to that of C. These results demonstrate for doxazosin an inhibitory effect on oxidative stress related proteins at gene and protein level, which confirms at molecular level a powerful antioxidant potential for this agent that could translate, in the long term, into a powerful antiatherosclerotic effect.
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PMID:Effect of doxazosin on oxidative stress related proteins in essential hypertensive patients. 1654 43

It has been reported that a substantial majority of hypertensives receive insufficient blood pressure (BP) control. As combination therapy for the treatment of hypertension, Ca channel blockers (CCBs), angiotensin II (AII) receptor blockers (ARBs), and/or AII-converting enzyme (ACE) inhibitors are mainly prescribed, while the efficacy of alpha(1)-blockers in such combination therapy remains unknown. The aim of this study was to investigate the efficacy of a low dose of an alpha(1)-blocker added to combination therapy with CCBs and either ARBs or ACE inhibitors for the treatment of hypertension. Subjects were 41 hypertensive patients (23 women and 18 men, mean age 66+/-12 years) who had been followed at the National Kyushu Medical Center. All patients showed poor BP control despite haven taken a combination of CCBs and ARBs or ACE inhibitors for more than 3 months. Doxazosin at a dose of 1 to 2 mg was added to each treatment regimen. The changes in various clinical parameters, including BP and blood chemistry, following the addition of doxazosin were then evaluated. The mean follow-up period was 170 days. BP decreased from 152+/-14/81+/-12 mmHg to 135+/-14/70+/-11 mmHg after the addition of doxazosin at a mean dose of 1.5 mg/day (p<0.001). When good systolic blood pressure (SBP) control was defined as <140 mmHg, the prevalence of patients with good SBP control increased from 24% to 61% (p<0.01). Similarly, the prevalence of patients with good diastolic blood pressure (DBP) control (<90 mmHg) increased from 78% to 98% (p<0.01). Patients whose SBP decreased more than 10 mmHg (n=25) showed significantly higher baseline SBP, serum total cholesterol and low-density lipoprotein (LDL) cholesterol levels compared to those who showed less SBP reduction (<10 mmHg) (n=16, p<0.01). Comparable BP reductions were obtained between obese (body mass index [BMI] > or =25, DeltaBP at 3 months: -15+/-15/-12+/-9 mmHg, n=18) and non-obese (BMI<25, DeltaBP: -14+/-19/-7+/-8 mmHg, n=23) patients. The results suggest that addition of a low dose of the alpha(1)-blocker doxazosin effectively reduces BP in patients taking CCBs and ARBs or ACE inhibitors. Thus, doxazosin seems to be useful as a third-line antihypertensive drug.
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PMID:Usefulness of the alpha1-blocker doxazosin as a third-line antihypertensive drug. 1754 Dec 8

Doxazosin mesylate is a selective alpha-adrenoreceptor antagonist for the treatment of hypertension and benign prostatic hyperplasia. A simple high performance liquid chromatographic method has been developed and validated for the quantitative determination of doxazosin in plasma. A reversed phase C18 column was used for the separation of doxazosin and prazosin (internal standard) with a mobile phase composed of water, acetonitrile, triethylamine (68:32:0.2 v/v, pH 5.0) at a flow rate of 1.2 mL/min. The fluorescence detector was operated at 246 (excitation) and 389 nm (emission). Intra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification of 1 ng/mL. Recovery of doxazosin from human plasma was greater than 93.4%. Doxazosin was stable in human plasma under various storage conditions. This method was used successfully for a pharmacokinetic study in plasma after oral administration of multiple 4-mg dose of doxazosin gastrointestinal therapeutic system formulation to 16 healthy volunteers. At steady state the mean area under the curve for a dosing interval and elimination half-life were calculated to be 367.0 +/- 63.5 ng x hr/mL and 29.2 +/- 4.5 hr, respectively. There was no difference in pharmacokinetic parameters between male and female.
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PMID:Pharmacokinetics of doxazosin gastrointestinal therapeutic system after multiple administration in Korean healthy volunteers. 1772 99

Metabolic syndrome, a cluster of metabolic abnormalities with visceral obesity and insulin resistance as its central component, is highly prevalent among hypertensive patients. Hypertension complicated by metabolic syndrome is associated with an increased risk of cardiovascular disease and new-onset Type II diabetes mellitus that further aggravates the prognostic outlook. Such a complex condition requires a multifactorial intervention including blood pressure lowering, improvement of the adverse metabolic profile and delayed onset of new diabetes. In this respect, doxazosin and other alpha-1 adrenoceptor blocking agents are of interest given their effect on the lipid profile in dyslipidemic, obese hypertensive patients, either diabetic or not. Doxazosin improves insulin sensitivity, apparently by accelerating insulin and glucose disposal through vasodilatation of skeletal muscle vascular beds. Whether long-term treatment with the drug might delay, or possibly prevent, incident Type II diabetes in hypertension complicated by metabolic syndrome is an intriguing possibility to be tested in appropriately designed clinical trials.
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PMID:Doxazosin in metabolically complicated hypertension. 1803 18

High morning blood pressure is related to target organ damage and future cardiovascular events. Chronobiologic therapies focusing on the early morning period may be an important strategy for antihypertensive therapy. The aim of this study was to clarify the add-on effects of bedtime dosing of the alpha(1)-adrenergic receptor antagonist doxazosin on morning blood pressure in patients with essential hypertension who were under long-acting calcium channel blocker amlodipine monotherapy. The add-on effects of doxazosin at the maximum dose of 6 mg at bedtime on home blood pressure and left ventricular geometry for 1 year were investigated in 49 subjects (37 men and 12 women, aged 57.5+/-9.1 years) with morning hypertension who had been treated with amlodipine alone for more than 1 year. Doxazosin induced a significant decrease in morning blood pressure (145.6+/-5.6/91.5+/-5.4 to 132.4+/-3.7/83.6+/-5.6 mmHg, p<or=0.001/<0.001) without a change of evening blood pressure (128.9+/-5.1/79.8+/-5.1 to 127.7+/-6.0/78.8+/-6.2 mmHg, p=0.056/0.051). Left ventricular mass index (LVMI; 124.8+/-19.8 to 95.6+/-15.7 g/m(2), p<0.001), relative wall thickness (0.457+/-0.061 to 0.405+/-0.047, p<0.001) and homeostasis model assessment of the insulin resistance index (HOMA-IR; 2.62+/-1.43 to 1.33+/-0.75, p<0.001) were decreased after doxazosin therapy. A stepwise multivariate regression analysis revealed that the changes in morning systolic blood pressure (adjusted r(2)=34.9%, p<0.001) and HOMA-IR (adjusted r(2)=4.5%, p=0.046) were significant contributory factors to the change in LVMI after doxazosin therapy. These results suggest that bedtime dosing of doxazosin is useful for the control of morning blood pressure and regression of left ventricular hypertrophy.
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PMID:Add-on effect of bedtime dosing of the alpha(1)-adrenergic receptor antagonist doxazosin on morning hypertension and left ventricular hypertrophy in patients undergoing long-term amlodipine monotherapy. 1825 May 47

Five classes of antihypertensive drugs have proven efficacy in the prevention of cardiovascular morbidity and mortality. Among the remaining antihypertensives, the action of alpha-1-blockers is supported by most clinical evidence; however, in combination therapy, the published data concern their use as third-line drugs at the most. The data from patients with drug-resistant hypertension remain limited. The aim of our study was to evaluate the efficacy and safety of doxazosin in this clinical setting. Data from 97 patients with resistant hypertension treated by doxazosin were analysed retrospectively. Doxazosin was usually added as the fifth antihypertensive drug in individuals who were either unresponsive to or intolerant of the combination of other antihypertensives. The dose of doxazosin ranged from 2 to 16 mg/day. The mean duration of follow-up was 21+/-17 months. Adverse events related to doxazosin treatment were rare and led to discontinuation of the therapy in only five patients (5.2%). Data from 34 patients were subjected to analysis of efficacy. In this subgroup, doxazosin therapy led to the reduction of blood pressure from 159+/-20/92+/-14 to 126+/-16/73+/-10 mmHg. We found that doxazosin is a well-tolerated and effective drug for patients with resistant arterial hypertension who require a combination of multiple antihypertensive drugs.
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PMID:Doxazosin: safety and efficacy in the treatment of resistant arterial hypertension. 1935 15

Doxazosin, an alpha(1)-adrenergic receptor inhibitor, is commonly administered to patients with type 2 diabetes, hypertension and nephropathy. The impact of 3 months' doxazosin therapy on the prevalence of activated and regulatory T lymphocytes was analysed in this pilot study of men with type 2 diabetes (n = 10) who received doxazosin 4 mg/day in addition to their ongoing therapy. The prevalence of CD4(+), CD8(+), CD25(+) and CD69(+) cells at baseline and after 3 months of add-on therapy was determined. The prevalence of regulatory T-cells was detected by two different approaches: forkhead box P3 (FoxP3) positivity; and the number of CD4(+)CD25(+high) cells. During 3 months of doxazosin therapy, patients' blood pressure, blood glucose control and lipid profiles all significantly improved. Simultaneously, the prevalence of activated T-cells (CD4(+)CD69(+) and CD8(+)CD69(+) cells) decreased, whereas that of regulatory T-cells increased. These results indicate an immunomodulatory action of doxazosin in type 2 diabetic patients.
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PMID:Effect of 3 months of doxazosin therapy on T-cell subsets in type 2 diabetic patients. 2014 98

We experienced anesthesia of a patient with pheochromocytoma on chronic hemodialysis who developed severe hypotension resistant to vasopressors after induction of general anesthesia. She was presented for spine surgery for destructive arthropathy of the cervical spine. Doxazosin up to 0.5 mg x day(-1) was administered for five days preoperatively for alpha-adrenergic blokade and regular hemodialysis was continued until the day before surgery without change in dry body weight. Blood pressure (BP) was within normal limits preoperatively. After induction of anesthesia with propofol and fentanyl, the patient developed hypotension with systolic BP of 60 mmHg which was resistant to vasopressor treatment with phenylephrine and ephedrine. After 45 minutes of volume replacement and commencement of dopamine and norepinephrine administration via a central venous catheter, BP recovered, and the surgery proceeded without further incident. Hypertension due to pheochromocytoma can be masked by excessive reduction of intravascular volume by preoperative hemodialysis. In a hemodialysed patient harboring pheochromocytoma who undergoes a surgical procedure unrelated to adrenalectomy, preoperative alpha-adrenergic blockade and subsequent intravascular volume expansion by increasing dry weight is required to avoid severe intraoperative hypotension, as for the case of adrenalectomy in the same situation.
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PMID:[Anesthetic management of a patient with pheochromocytoma and end-stage renal disease]. 2056 Mar 77


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