losartan-potassium and Sleep-Wake-Disorders

The failure to lower systolic blood pressure at night (called non-dipping) and sleep apnea are both associated with adverse cardiovascular outcomes. Sleep apnea is a common cause of non-dipping blood pressure.. Sleep apnea increases night time blood pressure through enhanced cardiac pre-load, sleep disturbance and hypoxia. Hypoxia elicits increased levels of norepinephrine, endothelin and erythropoetin. Patients with sleep apnea tend to be elderly and obese, so they have poor endothelial nitric oxide release and blunted baroreflexes. They thus have several stimuli for high blood pressure and poor compensatory mechanisms to lower blood pressure.. Non-dipping patients without sleep apnea have evidence of volume overload and correct their blood pressure pattern in response to diuretics. Individuals with sleep apnea have evidence of increased cardiac pre-load from episodes of negative intrathoracic pressure. Their daytime blood pressure responds poorly to many drugs, but beta blockers may be effective. Their night time blood pressure responds only slightly to therapy of their sleep apnea with continuous positive airway pressure, even though continuous positive airway pressure decreases their norepinephrine, erythropoetin and endothelin levels.

Topics: Blood Pressure; Blood Volume; Cardiovascular Diseases; Circadian Rhythm; Endothelins; Erythropoietin; Humans; Hypertension; Kidney Diseases; Nitric Oxide; Racial Groups; Respiration, Artificial; Sleep Apnea Syndromes; Sleep Wake Disorders

Numerous animal studies and clinical trials have demonstrated that erythropoietin (EPO) has therapeutic effects in ischemic and degenerative diseases. However, few clinical trials have investigated the effect of EPO in Parkinson's disease (PD) patients. This study was an exploratory pilot study to investigate the effects of recombinant human EPO (rhEPO) on motor and non-motor symptoms (NMS) in PD patients.. A total of 26 PD patients at the Hanyang University Hospital were enrolled in the study. The participants were randomly assigned to rhEPO and placebo groups. The rhEPO group was infused intravenously (40,000 IU each) twice a week for 5 weeks. Clinical improvement was estimated using the Unified Parkinson's Disease Rating Scale-III (UPDRS-III), the NMS Scale (NMSS) and the 39-Item Parkinson's Disease Questionnaire (PDQ-39). [(18)F] N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) photon emission tomography (PET) scanning was performed on each participant at baseline and again after 12 months.. The rhEPO administration significantly improved the NMSS and PDQ-39 scores at 12 months. The UPDRS-III, which reflects motor function, did not change significantly after the rhEPO treatment. With the NMSS, the domains of cardiovascular autonomic function, sleep/fatigue, mood/cognition and attention/memory showed significant changes. None of the participants experienced any serious adverse effects.. We found that rhEPO had beneficial effects on NMS but not on motor function. Dopaminergic refractory NMS, such as cardiovascular autonomic dysfunction and cognition, showed improvement after the administration of rhEPO. Our results suggest that rhEPO might be a good candidate for the treatment of NMS in PD patients.

Topics: Aged; Aged, 80 and over; Brain; Cognition Disorders; Erythropoietin; Female; Humans; Male; Mental Disorders; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Prospective Studies; Single-Blind Method; Sleep Wake Disorders; Surveys and Questionnaires; Time Factors; Tomography, X-Ray Computed; Tropanes; Vascular Diseases

Systemic injection of erythropoietin (EPO) over several days reduces sleep fragmentation in patients with periodic limb movements in sleep (PLMS). However, there are no studies concerning the effects of EPO on spontaneous sleep. In this study, we determined the effects of intracerebroventricular (i.c.v.) administration of EPO on spontaneous rat sleep. Three doses of EPO (25, 75, and 125 ng) were injected i.c.v. at the onset of the dark period. All doses of EPO increased non-rapid eye movement sleep (NREMS). In addition, high and low doses of EPO (125 and 25 ng) increased rapid eye movement sleep (REMS), but the medium dose of EPO (75 ng) inhibited REMS. Electroencephalogram slow-wave activity during NREMS also increased following the two higher doses of EPO. In contrast, EPO injection during the light period failed to affect sleep. Brain temperature (Tbr) was not affected by any dose of EPO. These results suggest that EPO could be part of the cytokine network involved in sleep regulation.

Topics: Animals; Brain; Circadian Rhythm; Cytokines; Dose-Response Relationship, Drug; Erythropoietin; Injections, Intraventricular; Male; Photic Stimulation; Rats; Rats, Sprague-Dawley; Receptors, Erythropoietin; Sleep; Sleep Disorders, Circadian Rhythm; Sleep Wake Disorders; Sleep, REM

End-stage renal disease (ESRD) is commonly associated with complaints of disturbed sleep and sleep disorders, frequently related to periodic limb movements in sleep (PLMS) or sleep apnea that may result in daytime sleepiness and other sequelae. Improvements in quality of life, including subjective sleep quality, have been reported in ESRD patients treated with recombinant human erythropoietin (rHuEPO). We investigated the objective effects of normalizing hematocrit on sleep disorders, sleep patterns, and daytime ability to remain awake in ESRD patients. Ten hemodialysis patients with sleep complaints while on rHuEPO therapy were studied by polysomnography while moderately anemic (mean hematocrit, 32.3%) and again when hematocrit was normalized (mean hematocrit, 42.3%) by increased rHuEPO dosing. Sleep patterns and associated parameters were monitored. Delivered dialysis dose and iron storage factors were monitored. Maintenance of Wakefulness Testing (MWT) was performed to assess daytime alertness/sleepiness. All 10 subjects experienced highly statistically significant reductions in the total number of arousing PLMS (P = 0.002). Nine of 10 subjects showed reductions in both the Arousing PLMS Index (P < 0.01) and the PLMS Index (P = 0.03) when hematocrit was normalized. Measures of sleep quality showed trends to improved quality of sleep. MWT demonstrated significant improvement in the length of time patients were able to remain awake (9.7 versus 17.1 minutes; P = 0.04). RHuEPO therapy with full correction of anemia reduces PLMS, arousals from sleep, and sleep fragmentation while allowing for more restorative sleep and improved daytime alertness. These findings may explain one mechanism for the improved quality-of-life parameters reported in ESRD patients treated with rHuEPO.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Erythropoietin; Female; Hematocrit; Humans; Kidney Failure, Chronic; Male; Middle Aged; Polysomnography; Recombinant Proteins; Renal Dialysis; Sleep Wake Disorders