-
European Journal of Applied Physiology Dec 2023We sought to investigate the effect of the α1-adrenergic receptor blockade during handgrip exercise (Grip), isolated metaboreflex activation (Metabo), and cold pressor...
We sought to investigate the effect of the α1-adrenergic receptor blockade during handgrip exercise (Grip), isolated metaboreflex activation (Metabo), and cold pressor test (CPT) on coronary circulation in young (YW) and postmenopausal women (PMW). Ten YW and 9 PMW underwent two protocols: (1) 3 min of baseline followed by 3 min of CPT and (2) 3 min of rest, 3 min of Grip followed by 3 min of Metabo. Protocols were carried out under control conditions and α1-adrenergic receptor blockade (oral prazosin 0.03 mg·kg). Coronary blood velocity (CBV) and vascular conductance (CCI) were lower in PMW. Grip increased CBV only in YW (YW: Δ18.0 ± 21.1% vs. PMW: Δ4.2 ± 10.1%; p < 0.05), and the blockade did not change the CBV response to Grip in YW and PMW. During the Metabo, CBV returned to resting levels in YW and was unchanged from rest in PMW, before (YW:Δ1.7 ± 8.7% vs. PMW: Δ- 1.5 ± 8.6) and under the blockade (YW: Δ4.5 ± 14.8% vs. PMW: Δ9.1 ± 29.5%). CPT did not change CBV in both groups (YW: Δ3.9 ± 8.0 vs. PMW: Δ- 4.1 ± 6.2%), following the α1-blockade, CPT increased CBV only in YW (YW: Δ11.2 ± 12.8% vs. PMW: Δ2.2 ± 7.1%; p < 0.05 for group and condition). CCI decreased during Grip, Metabo, and CPT in YW and PMW, while the blockade prevented that decrease only in YW. The α1-adrenergic receptor plays a role in the control of coronary circulation in young women, evoking stronger vasoconstriction during CPT than Grip and Metabo in YW. PMW have impaired vasomotor control in the coronary circulation, which seems not to be caused by the α1-adrenergic receptor.
Topics: Humans; Female; Receptors, Adrenergic, alpha; Postmenopause; Hand Strength; Coronary Circulation; Prazosin
PubMed: 37368136
DOI: 10.1007/s00421-023-05267-4 -
Nigerian Journal of Physiological... Dec 2023Acute caffeine exposure had been shown to induce hyperglycemia however; the influence of thyroid hormones on the caffeine-induced hyperglycemia is yet to be established....
Acute caffeine exposure had been shown to induce hyperglycemia however; the influence of thyroid hormones on the caffeine-induced hyperglycemia is yet to be established. The present study was therefore designed to investigate the effect of caffeine exposure on blood glucose and hepatic glycogen content in thyroidectomized rats. Sixty adult male Wistar rats were randomly divided into 10 groups as I-X (n=6). Rats in groups I, III, V, VII and IX were given normal saline, caffeine, prazosin + caffeine, propranolol +caffeine, combined prazosin+ propranolol+caffeine injections respectively while rats in groups II, IV, VI, VIII and X were thyroidectomized and treated in similar manner as the normal rats respectively. Surgical removal of the thyroid gland was done in the thyroidectomised groups while sham-operation was done in Normal group to serve as control. After healing and following an overnight fast, the rats were anaesthetized and the femoral vein and carotid artery were cannulated for drug administration and blood glucose measurement respectively. After stabilization, following basal measurements, rats from each group were injected normal saline or caffeine (6mg/kg) while another sets were pre-treated prazosin (0.2 mg/kg), propanolol (0.5 mg/kg) or their combination before caffeine administration. Blood glucose was then monitored for 60 minutes post-injection of caffeine at 5 minutes interval. Liver samples were collected at the end of the observation period for glycogen content determination. Caffeine caused significant increased blood glucose levels in both normal and thyroidectomized rats which were up to 210% and 180% respectively at the peak of their responses. Liver glycogen content of the thyroidectomized rats (3.11 ± 0.20 mg/100g tissue weight) was significantly higher than the normal rats (1.91 ± 0.43 mg/100g tissue weight). These glycogen contents were significantly reduced by caffeine in both normal (0.25 ± 0.04 mg/100g tissue weight) and thyroidectomized rats (1.65 ± 0.16 mg/100g tissue weight) when compared with their controls. The caffeine effects on blood glucose and hepatic glycogen content were abolished by pretreatment with propanolol or a combination of prazosin and propanolol in both normal and thyroidectomized rats but pretreatment with prazosin caused only significant reduction in hyperglycemic response to caffeine. The findings of this study suggest that caffeine-induced hyperglycemia in both normal and thyroidectomized rats are mediated through both alpha and beta adrenoceptors.
Topics: Animals; Male; Rats, Wistar; Caffeine; Thyroidectomy; Blood Glucose; Liver Glycogen; Rats; Liver; Prazosin; Propranolol; Hyperglycemia; Glycogen
PubMed: 38696689
DOI: 10.54548/njps.v38i2.8 -
European Journal of Psychotraumatology 2024Clonidine is a centrally acting anti-adrenergic agent that may have applications in post-traumatic stress disorder (PTSD), particularly for sleep. In this systematic... (Review)
Review
Clonidine is a centrally acting anti-adrenergic agent that may have applications in post-traumatic stress disorder (PTSD), particularly for sleep. In this systematic review, we aimed to summarize the effect of clonidine on sleep quality and duration, nightmares, and PTSD symptom severity in adults with PTSD. PubMed (Medline), Embase, PsycINFO, CINAHL, and clinicaltrials.gov were searched up to April 2023. Studies on clonidine use in adult PTSD patients reporting data on the effect on sleep, nightmares, and PTSD symptoms were included. A narrative summary and a meta-analysis of the study findings are presented. Ten reports, accounting for = 569 patients with PTSD (145 on clonidine and 436 controls), were included in the final selection. There were four case reports, four observational studies, one non-blind clinical trial, and one crossover randomized controlled trial (RCT). Median clonidine dose was 0.15 mg/day (range: 0.1-0.5 mg/day). Median follow-up time was 31 days (range: 3 days to 19 months). The quality of the evidence was rated from very low to low. There was marked between-study heterogeneity and low power in the individual studies, but many reported improved sleep quality, nightmare reduction, and improvement of PTSD symptoms for patients treated with clonidine. Meta-analysis was only possible for two studies reporting the effect of clonidine on nightmares, and showed no difference from the comparator (i.e. prazosin or terazosin) (odds ratio: 1.16; 95% confidence interval: 0.66 to 2.05), potentially pointing towards non-inferiority between these medications. Future research, such as well-powered RCTs, is needed to identify the efficacy in the lower dose range and the most suitable treatment group, and to obtain good evidence on the effects of clonidine in the treatment of sleep disorders related to PTSD.
Topics: Clonidine; Humans; Stress Disorders, Post-Traumatic; Dreams; Sleep Quality; Adrenergic alpha-2 Receptor Agonists
PubMed: 38941125
DOI: 10.1080/20008066.2024.2366049 -
Pharmaceuticals (Basel, Switzerland) Oct 2023Major depressive disorder is a severe mood disorder characterized by different emotions and feelings. This study investigated the antidepressant activity of the...
Major depressive disorder is a severe mood disorder characterized by different emotions and feelings. This study investigated the antidepressant activity of the phenylpropanoid methyleugenol (ME) in adult female mice exposed to a stress model induced by dexamethasone. The animals were randomly divided into groups containing eight animals and were pre-administered with dexamethasone (64 μg/kg subcutaneously). After 165 and 180 min, they were treated with ME (25, 50 and 100 mg/kg intraperitoneally) or imipramine (10 mg/kg intraperitoneally) after 45 min and 30 min, respectively; they were then submitted to tests which were filmed. The videos were analyzed blindly. In the tail suspension test, ME (50 mg/kg) increased latency and reduced immobility time. In the splash test, ME (50 mg/kg) decreased grooming latency and increased grooming time. In the open field, there was no statistical difference for the ME groups regarding the number of crosses, and ME (50 mg/kg) increased the number of rearing and time spent in the center. Regarding in silico studies, ME interacted with dopaminergic D1 and α1 adrenergic pathway receptors and with tryptophan hydroxylase inhibitor. In the in vivo evaluation of the pathways of action, the antidepressant potential of ME (50 mg/kg) was reversed by SCH23390 (4 mg/kg intraperitoneally) dopaminergic D1 receptor, Prazosin (1 mg/kg intraperitoneally) α1 adrenergic receptor, and PCPA (4 mg/kg intraperitoneally) tryptophan hydroxylase inhibitor. Our findings indicate that ME did not alter with the locomotor activity of the animals and shows antidepressant activity in female mice with the participation of the D1, α1 and serotonergic systems.
PubMed: 37895879
DOI: 10.3390/ph16101408 -
Sleep Medicine Oct 2023Rapid eye movement sleep (REMS) is essential for leading normal healthy living at least in higher-order mammals, including humans. In this review, we briefly survey the... (Review)
Review
Rapid eye movement sleep (REMS) is essential for leading normal healthy living at least in higher-order mammals, including humans. In this review, we briefly survey the available literature for evidence linking cytomorphometric changes in the brain due to loss of REMS. As a mechanism of action, we add evidence that REMS loss elevates noradrenaline (NA) levels in the brain, which affects neuronal cytomorphology. These changes may be a compensatory mechanism as the changes return to normal after the subjects recover from the loss of REMS or if during REMS deprivation, the subjects are treated with NA-adrenoceptor antagonist prazosin (PRZ). We had proposed earlier that one of the fundamental functions of REMS is to maintain the level of NA in the brain. We elaborate on this idea to propose that if REMS loss continues without recovery, the sustained level of NA breaks down neurophysiologically active compensatory mechanism/s starting with changes in the neuronal cytomorphology, followed by their degeneration, leading to acute and chronic pathological conditions. Identification of neuronal cytomorphological changes could prove to be of significance for predicting future neuronal (brain) damage as well as an indicator for REMS health. Although current brain imaging techniques may not enable us to visualize changes in neuronal cytomorphology, given the rapid technological progress including use of artificial intelligence, we are optimistic that it may be a reality soon. Finally, we propose that maintenance of optimum REMS must be considered a criterion for leading a healthy life.
Topics: Animals; Humans; Sleep, REM; Artificial Intelligence; Brain; Sleep Deprivation; Prazosin; Mammals
PubMed: 37524037
DOI: 10.1016/j.sleep.2023.07.022 -
The Journal of the Association of... Apr 2024The isometric handgrip (IHG) test is commonly used to detect sympathetic autonomic dysfunction. Tamsulosin, approved for the management of symptomatic benign prostatic... (Observational Study)
Observational Study
Effect of α-blockers on Handgrip Test Response of Diastolic Blood Pressure in Hypertensive, Benign Hypertrophy of Prostate Patients in a Therapeutics Clinic, Kolkata: A Cross-sectional Study.
BACKGROUND
The isometric handgrip (IHG) test is commonly used to detect sympathetic autonomic dysfunction. Tamsulosin, approved for the management of symptomatic benign prostatic hyperplasia (BPH), acts as an antagonist for α1-adrenergic receptors (α1-AR), whereas prazosin, an α receptor blocker, being less selective than tamsulosin, is used as an antihypertensive agent clinically. Our objective was to investigate if there is a distinction in blood pressure (BP) increase during IHG exercise between individuals with essential hypertension taking tamsulosin compared to those taking prazosin.
MATERIALS AND METHODS
A cross-sectional observational study was performed on 50 subjects receiving tablet prazosin and 47 subjects receiving tamsulosin, who were asked to undergo an IHG test. Pre- and posttest BP was recorded for both the groups, and the difference in diastolic BP (DBP) (delta DBP) was compared between the groups and to their respective baseline values.
RESULTS
Post-IHG test, mean DBP was found to be 93.98 ± 9.13 mm Hg in the prazosin group and 101.00 ± 12.05 mm Hg in the tamsulosin group, respectively. The change of delta DBP in the tamsulosin group was significant, but the prazosin group showed an insignificant rise in DBP.
CONCLUSION
Prazosin, being less selective than tamsulosin in terms of α1 receptor antagonism, showed suppression of BP during IHG. Tamsulosin demonstrates high selectivity for prostatic receptors while showing minimal affinity for vascular receptors. As a result, its impact on BP is expected to be minimal.
Topics: Humans; Male; Cross-Sectional Studies; Prostatic Hyperplasia; Prazosin; Tamsulosin; Middle Aged; Adrenergic alpha-1 Receptor Antagonists; Blood Pressure; Hypertension; Hand Strength; Aged; Antihypertensive Agents; India
PubMed: 38881078
DOI: 10.59556/japi.72.0501 -
Naunyn-Schmiedeberg's Archives of... May 20246-Nitrodopamine (6-ND) is released from human vas deferens and plays a modulatory role in the male ejaculation. Therapeutical use of α-adrenoceptor antagonists is...
6-Nitrodopamine (6-ND) is released from human vas deferens and plays a modulatory role in the male ejaculation. Therapeutical use of α-adrenoceptor antagonists is associated with ejaculatory abnormalities. To evaluate the effect of α-adrenoceptor antagonists on the contractions induced by 6-ND, dopamine, noradrenaline, and adrenaline in the human epididymal vas deferens (HEVD). HEVD strips were suspended in glass chambers containing heated and oxygenated Krebs-Henseleit's solution. Cumulative concentration-response curves to catecholamines (10 nM-300 μM) were constructed in HEVD strips pre-incubated (30 min) with doxazosin (0.1-1 nM), tamsulosin (1-10 nM), prazosin (10-100 nM) and/or silodosin (0.1-10 nM). The effects of these α-adrenoceptor antagonists were also evaluated in the electric-field stimulation (EFS, 2-32 Hz)-induced contractions. Doxazosin (0.1 nM) caused significant reductions in 6-ND-induced HEVD contractions without affecting the contractions induced by dopamine, noradrenaline, and adrenaline. Similar results were observed with tamsulosin (1 nM) and prazosin (10 nM). At these concentrations, these α-adrenoceptor antagonists largely reduced the EFS-induced contractions. Silodosin (1 nM) caused concentration-dependent rightward shifts of the concentration-response curves to 6-ND but had no effect on the contractions induced by dopamine and adrenaline. Silodosin (0.1 nM) only inhibited the contractions induced by noradrenaline. Silodosin at 1 nM, but not at 0.1 nM, caused significant reductions in the EFS-induced contractions. The results reinforce the concept that 6-ND plays a major role in the human vas deferens contractility and indicate that the ejaculation disorders caused by doxazosin, tamsulosin, prazosin and silodosin cause in man, may be due to inhibition of the contractions induced by 6-ND rather than by the classical catecholamines dopamine, noradrenaline, and adrenaline.
Topics: Male; Humans; Vas Deferens; Adrenergic alpha-1 Receptor Antagonists; Muscle Contraction; Epinephrine; In Vitro Techniques; Norepinephrine; Dose-Response Relationship, Drug; Doxazosin; Middle Aged; Adult; Prazosin; Tamsulosin; Dopamine; Electric Stimulation; Indoles; Aged; Sulfonamides
PubMed: 37910185
DOI: 10.1007/s00210-023-02805-x -
Peptides Aug 2023Excessive activation of the sympathetic nervous system is involved in cardiovascular damage including cardiac hypertrophy. Natriuretic peptides are assumed to exert...
Excessive activation of the sympathetic nervous system is involved in cardiovascular damage including cardiac hypertrophy. Natriuretic peptides are assumed to exert protective actions for the heart, alleviating hypertrophy and/or fibrosis of the myocardium. In contrast to this assumption, we show in the present study that both atrial and C-type natriuretic peptides (ANP and CNP) potentiate cardiac hypertrophic response to noradrenaline (NA) in rats. Nine-week-old male Wistar rats were continuously infused with subcutaneous 30 micro-g/h NA without or with persistent intravenous administration of either 1.0 micro-g/h ANP or CNP for 14 days. Blood pressure (BP) was recorded under an unrestrained condition by a radiotelemetry system. Cardiac hypertrophic response to NA was evaluated by heart weight/body weight (HW/BW) ratio and microscopic measurement of myocyte size of the left ventricle. Mean BP levels at the light and dark cycles rose by about 20 mmHg following NA infusion for 14 days, with slight increases in HW/BW ratio and ventricular myocyte size. Infusions of ANP and CNP had no significant effects on mean BP in NA-infused rats, while two natriuretic peptides potentiated cardiac hypertrophic response to NA. Cardiac hypertrophy induced by co-administration of NA and ANP was attenuated by treatment with prazosin or atenolol. In summary, both ANP and CNP potentiated cardiac hypertrophic effect of continuously infused NA in rats, suggesting a possible pro-hypertrophic action of natriuretic peptides on the heart.
Topics: Rats; Animals; Male; Rats, Wistar; Norepinephrine; Atrial Natriuretic Factor; Cardiomegaly; Blood Pressure; Natriuretic Peptide, C-Type; Natriuretic Peptide, Brain
PubMed: 37263541
DOI: 10.1016/j.peptides.2023.171035 -
Cureus Jul 2023Objectives Post-traumatic stress disorder (PTSD) symptoms are reported in over 36% of individuals with bulimia nervosa. To date, none of the clinical trials have...
Objectives Post-traumatic stress disorder (PTSD) symptoms are reported in over 36% of individuals with bulimia nervosa. To date, none of the clinical trials have examined nightmare reduction in this population. We evaluated the effectiveness of prazosin in bulimic females experiencing PTSD-related nightmares. We hypothesized that prazosin will decrease nightmares, normalize cortisol levels and secretory patterns, and improve sleep. Methods Our seven-week prospective, randomized, double-blind, placebo-controlled crossover pilot trial recruited eight adult women. Each participant received three weeks of prazosin and a placebo, separated by a one-week washout period. The order of treatment was counterbalanced across participants. Self-reports, clinician-administered scales, and salivary cortisol was collected to measure outcomes. Results A significant treatment effect was seen in nightmare intensity on the Clinician-Administered PTSD Scale (CAPS-I) (p=0.026) and a marginally significant effect on nightmare frequency (p=0.069). The only significant main effect of treatment on self-reported sleep parameters was on nightmares. Cortisol secretory patterns did not change, but on average, study participants had significantly higher cortisol levels compared to normative values. ANOVA showed a significant main effect of time for cortisol (F(4, 28) = 6.15, p=.001) but no within or between groups significant effects (ps>.179). Follow-up tests showed the effect of time was linear (F(1, 7) = 10.77, p=.013). Conclusion Prazosin significantly reduced intensity and marginally reduced the frequency of PTSD-related nightmares in bulimia nervosa but did not affect subjective sleep efficiency, quality, cortisol levels, or diurnal cortisol secretory pattern. Larger trials using objective sleep measures are warranted to replicate these findings.
PubMed: 37637523
DOI: 10.7759/cureus.42433 -
Naunyn-Schmiedeberg's Archives of... Apr 2024Quercetin, a plant-derived flavonoid, is an antioxidant and has demonstrated antidepressant and anti-inflammatory activities in several animal models. However, there is...
Quercetin, a plant-derived flavonoid, is an antioxidant and has demonstrated antidepressant and anti-inflammatory activities in several animal models. However, there is scanty information on the underlying mechanisms of its antidepressant property. This present study aimed at assessing the involvement of monoaminergic systems in the antidepressant-like activity of quercetin in experimental animals. Mice received varying doses of quercetin (25, 50 &100 mg/kg daily) and were then subjected to open field test (OPF), despair tests, the reserpine test, and the yohimbine lethality test (YLT). In addition, monoaminergic involvement was investigated by combining quercetin (100 mg/kg) with dopaminergic antagonists (haloperidol and sulpiride), adrenergic blockers (prazosin, propranolol and yohimbine), and serotonergic blockers/inhibitors (metergoline). The results showed that quercetin produced significant anti-immobility effects in the forced swim test (FST) and tail suspension test (TST), suggesting antidepressant activity. In addition, the potentiation of yohimbine lethality by quercetin further indicates its antidepressant-like property. This antidepressant action demonstrated was, however, blocked when quercetin was co-administered with dopaminergic, adrenergic and serotonergic antagonists, suggesting involvement of the monoaminergic system in the antidepressant action of quercetin. Nevertheless, quercetin did not significantly alter the locomotor activity of mice, which implies lack of stimulant effect. Taken together, these outcomes suggest that monoaminergic systems are likely involved in the anti-depressant effect of quercetin in mice.
Topics: Animals; Mice; Quercetin; Biogenic Monoamines; Antidepressive Agents; Sulpiride; Yohimbine; Swimming; Hindlimb Suspension; Depression; Behavior, Animal
PubMed: 37851059
DOI: 10.1007/s00210-023-02789-8