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Aim/Objective: We report a case of priapism probably induced by sertraline. Methods: Not applicable. Results: A 56-year-old man patient who was admitted to the emergency department due to prolonged painful erection. His past medical history included bipolar disorder since 20-year managed with lamotrigine, amitriptyline, and bromazepam. He had not experienced any sexual disorders under antipsychotics listed above. Sertraline was added to his medication regimen 3 months ago. According to the patient, erection had occurred spontaneously. There was no sexual stimulation and the patient denied any history of perineal or other penile trauma. He was not taking any drugs for erectile dysfunction and he denied illicit drugs intake, including cocaine and methamphetamine. In the emergency room, the patient was afebrile and hemodynamically stable. The patient's physical exam revealed painful penile erection with testicles pain. Laboratory tests including complete cell count were within normal limits. No evidence of disease can induce priapism such as multiple myeloma, sickle cell anemia, or thalassemia. In urological unit and under hemodynamic monitoring, the patient received normal saline irrigation in corpus cavernosum with 2 mg of phenylephrine instilled gradually with no decrease of rigidity. In front of poor response to medical treatment, the patient was brought to the operating room for caverno-spongiosal shunting. The surgical shunt was performed with no improvement of priapism. Therefore, drug-induced priapism was suspected and sertraline (the last drug introduced) was withdrawn and priapism was regressed progressively. The other medications were continued without incident. Conclusion: Priapism is a rare but serious side effect of antipsychotics drugs including SSRI medications. Clinicians should be aware that the use of drug combinations with alpha-1 adrenergic receptor blocking propertie may increase the risk of priapism.

Hyperactivity of the sympathetic nervous system is a major driver of cardiac remodeling, exerting its effects through both α-, and β-adrenoceptors (α-, β-ARs). As the relative contribution of subtype α1-AR to cardiac stress responses remains poorly investigated, we subjected mice to either subcutaneous perfusion with the β-AR agonist isoprenaline (ISO, 30 mg/kg × day) or to a combination of ISO and the stable α1-AR agonist phenylephrine (ISO/PE, 30 mg/kg × day each). Telemetry analysis revealed similar hemodynamic responses under both ISO and ISO/PE treatment i.e., permanently increased heart rates and only transient decreases in mean blood pressure during the first 24 h. Echocardiography and single cell analysis after 1 week of exposure showed that ISO/PE-, but not ISO-treated animals established α1-AR-mediated inotropic responsiveness to acute adrenergic stimulation. Morphologically, additional PE perfusion limited concentric cardiomyocyte growth and enhanced cardiac collagen deposition during 7 days of treatment. Time-course analysis demonstrated a diverging development in transcriptional patterns at day 4 of treatment i.e., increased expression of selected marker genes Xirp2, Nppa, Tgfb1, Col1a1, Postn under chronic ISO/PE treatment which was either less pronounced or absent in the ISO group. Transcriptome analyses at day 4 via RNA sequencing demonstrated that additional PE treatment caused a marked upregulation of genes allocated to extracellular matrix and fiber organization along with a more pronounced downregulation of genes involved in metabolic processes, muscle adaptation and cardiac electrophysiology. Consistently, transcriptome changes under ISO/PE challenge more effectively recapitulated early transcriptional alterations in pressure overload-induced experimental heart failure and in human hypertrophic cardiomyopathy.

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension (HT), and is associated with a higher cardiometabolic risk than essential HT. However, PA remains underdiagnosed, probably due to several difficulties clinicians usually find in performing its diagnosis and subtype classification. The aim of this consensus is to provide practical recommendations focused on the prevalence and the diagnosis of PA and the clinical implications of aldosterone excess, from a multidisciplinary perspective, in a nominal group consensus approach by experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology, Spanish Association of Surgeons (AEC). Highlights Following a positive screening test, no further studies are needed for diagnosis of PA if a plasma aldosterone concentration (PAC) > 20 ng/dL and a low circulating direct renin or plasma renin activity (PRA) are detected in a patient with spontaneous hypokalemia. In all other patients, one (or more) of four different tests is (are) currently recommended: the fludrocortisone suppression test, the oral salt loading test, the intravenous saline test, and/or the captopril challenge test. In all cases, hypokalemia must be corrected prior to testing. Interfering medication must be progressively withdrawn before testing, while introducing alpha-1 adrenergic blockers, long-acting non-dihydropyridine calcium antagonists, and/or hydralazine as needed for control of hypertension. All but the captopril challenge test run the risk of inducing hypokalemia, fluid overload, and a worsening of hypertension. In the case of borderline results, the initial test employed can be repeated, or a second test performed. Patients with both a negative saline infusion and captopril challenge test appear to be at a low risk for harboring unilateral disease, whereas those positive for both are more likely to exhibit unilateral aldosterone secretion than when tests render conflicting results. Patients showing a positive screening aldosterone to renin ratio (ARR) with normal/high PAC and a low renin/PRA, yet with negative diagnostic testing, presenting mild hyperaldosteronism, can benefit from targeted therapy of hypertension with mineralocorticoid receptor antagonists.

Decreased sperm quality has been reported in men with different clinical conditions, including aging and hypertension. In the male reproductive tract, it has been suggested that the α1-adrenergic receptor influences fertility and spermatogenesis, and important functions are also attributed to the renin–angiotensin axis, such as regulation of steroidogenesis, spermatogenesis, and sperm function. Previously, our group demonstrated impaired testicular vasomotion via α1-adrenergic receptor activation and increased hypoxia-related proteins in the testes of spontaneously hypertensive rats (SHRs) compared to Wistar normotensive rats. In this study, we aimed to investigate the effect of hypertension and inhibition of systemic α1-adrenergic receptor or angiotensin II AT1 receptor on sperm quality, sperm functional characteristics, and testicular microcirculation in rats from three different ages: young (8–10-week-old), adult (20–24-week-old) and older adult (60–66-week-old). We observed higher blood pressure in SHRs of all ages compared to age-matched Wistar rats. Lower blood pressure was observed either in prazosin or losartan-treated adult or aged SHRs. Additionally, lower sperm concentration, impaired motility and higher acrosome damage were demonstrated in SHRs. Prazosin treatment alleviated the effects of hypertension on sperm concentration and motility but not acrosome damage. Higher vasomotion was noticed in testicular blood vessels of adult and aged SHRs compared to Wistar rats. Thus, impaired sperm quality was observed in SHRs of different ages and was improved by sub-chronically blocking the α1-adrenergic receptor.

Purpose Resting beat-to-beat blood pressure variability is a strong predictor of cardiovascular events and mortality. However, its underlying mechanisms remain incompletely understood. Given that the sympathetic nervous system plays a pivotal role in cardiovascular regulation, we hypothesized that alpha-1 adrenergic receptors (the main sympathetic receptor controlling peripheral vasoconstriction) may contribute to resting beat-to-beat blood pressure variability. Methods Beat-to-beat heart rate (electrocardiography) and blood pressure (photoplethysmography) were continuously measured before and 2 h following, selective blockade of alpha-1 adrenergic receptors via oral administration of prazosin (1 mg/20 kg) in ten young healthy adults (two women). Cardiac output and total peripheral resistance were estimated using the ModelFlow method. Results Selective blockade of alpha-1 adrenergic receptors was confirmed by the marked reduction in the pressor response to intravenous infusion of phenylephrine hydrochloride (−80 ± 15%, P  = 0.001 versus pre-prazosin). The blockade significantly decreased the standard deviation of the systolic (pre-prazosin versus post-prazosin: 5.6 ± 1.4 versus 3.8 ± 0.7 mmHg, P  = 0.002), diastolic (3.2 ± 1.2 versus 2.2 ± 0.5 mmHg, P  = 0.022), and mean blood pressure (3.7 ± 1.2 versus 2.5 ± 0.5 mmHg, P  = 0.009), as well as total peripheral resistance (0.8 ± 0.5 versus 0.5 ± 0.1 mmHg/L/min, P  = 0.047), but not cardiac output (521 ± 188 versus 453 ± 160 mL/min, P  = 0.321). Similar results were found using different indices of variability. Conclusion These findings indicate that alpha-1 adrenergic receptors play a significant role in regulating resting beat-to-beat blood pressure variability in young, healthy adults.

Inguinal hernioplasty is a common surgical procedure, often associated with complications such as post-operative urinary retention (POUR). POUR, characterized by an inability to urinate despite a full bladder following a surgery that may need foley catheterization that on its own can lead to urinary tract infection, stricture, prolonged hospitalization, and increases cost of hospital care. Tamsulosin is a selective alpha-1 adrenergic blocker that can increase urine flow by relaxing the smooth muscle of urethra and prostate, thereby as a less invasive method may be effective in prevention of POUR. This randomized clinical trial involved 179 male participants over 50 undergoing unilateral hernioplasty under spinal anesthesia. Group A (87 subjects) received 0.4 ​mg Tamsulosin 8 ​h before surgery, then 6–12 ​h post-operatively. Group B (92 subjects) received a placebo on the same schedule. Both were monitored for POUR incidence within 24 ​h post-surgery. Data were analyzed using SPSS software version 18 and the P ​< ​0.05 was considered statistically significant. The mean age of participants was 63.37 ​± ​10.62 years. POUR requiring catheterization occurred in 10.3 ​% of Group A and 16.3 ​% of Group B. However, the difference was not statistically significant (p ​= ​0.242). Logistic regression showed no significant prophylactic effect of Tamsulosin (p ​= ​0.171), hypertension (p ​= ​0.166), diabetes mellitus (p ​= ​0.196), or benign prostatic hyperplasia (p ​= ​0.273) on POUR incidence. Prophylactic Tamsulosin did not significantly reduce the incidence of POUR following inguinal hernioplasty under spinal anesthesia. •And is registered in Iranian Registry of Clinical Trial under registration number [IRCT20220131053898N1].•Although a prospective power analysis was not conducted prior to initiating the trial, the sample size was estimated based on prior similar randomized studies and the expected number of eligible patients during the planned enrollment period. We acknowledge this as a limitation and plan to incorporate formal power analysis in future study designs.•Although a prospective power analysis was not conducted, the study achieved statistically significant outcomes. Nonetheless, we acknowledge this as a limitation and recommend that future trials include formal power calculations during the design phase.

We developed, characterized and validated nLight sensors, a new family of genetically encoded green and red fluorescent norepinephrine indicators based on an alpha-1 adrenergic receptor. nLight probes can detect norepinephrine in living animals with superior sensitivity, ligand specificity and temporal resolution as compared with previous tools.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death amongst patients whose seizures are not adequately controlled by current therapies. Patients with SCN8A encephalopathy have an elevated risk for SUDEP. While transgenic mouse models have provided insight into the molecular mechanisms of SCN8A encephalopathy etiology, our understanding of seizure-induced death has been hampered by the inability to reliably trigger both seizures and seizure-induced death in these mice. Here, we demonstrate that mice harboring an Scn8a allele with the patient-derived mutation N1768D (D/+) are susceptible to audiogenic seizures and seizure-induced death. In adult D/+ mice, audiogenic seizures are non-fatal and have nearly identical behavioral, electrographical, and cardiorespiratory characteristics as spontaneous seizures. In contrast, at postnatal days 20–21, D/+ mice exhibit the same seizure behavior, but have a significantly higher incidence of seizure-induced death following an audiogenic seizure. Seizure-induced death was prevented by either stimulating breathing via mechanical ventilation or by acute activation of adrenergic receptors. Conversely, in adult D/+ mice inhibition of adrenergic receptors converted normally non-fatal audiogenic seizures into fatal seizures. Taken together, our studies show that in our novel audiogenic seizure-induced death model adrenergic receptor activation is necessary and sufficient for recovery of breathing and prevention of seizure-induced death.

Exosomes, biologically active nanoparticles (40-100 nm) released by hematopoietic and non-hematopoietic cells, contain a variety of proteins and small, non-coding RNA known as microRNA (miRNA). Exposure to various pathogens and disease states modifies the composition and function of exosomes, but there are no studies examining in vivo exosomal changes evoked by the acute stress response. The present study reveals that exposing male Fisher 344 rats to an acute stressor modulates the protein and miRNA profile of circulating plasma exosomes, specifically increasing surface heat shock protein 72 (Hsp72) and decreasing miR-142-5p and -203. The selected miRNAs and Hsp72 are associated with immunomodulatory functions and are likely a critical component of stress-evoked modulation of immunity. Further, we demonstrate that some of these stress-induced modifications in plasma exosomes are mediated by sympathetic nervous system (SNS) activation of alpha-1 adrenergic receptors (ADRs), since drug-mediated blockade of the receptors significantly attenuates the stress-induced modifications of exosomal Hsp72 and miR-142-5p. Together, these findings demonstrate that activation of the acute stress response modifies the proteomic and miRNA profile of exosomes released into the circulation.

In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor (⍺ 1 -AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n = 18,547) and three cohorts with pneumonia (n = 400,907). Federated across two ARD cohorts, we find that patients exposed to ⍺ 1 -AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR = 0.70, p = 0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of ⍺ 1 -AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.