Cardiovascular Effects Mediated by Imidazoline Drugs: An Update

Author(s):  
Luis Cobos-Puc ◽  
Hilda Aguayo-Morales

Objective: Clonidine is a centrally acting antihypertensive drug. Hypotensive effect of clonidine is mediated mainly by central α2-adrenoceptors and/or imidazoline receptors located in a complex network of the brainstem. Unfortunately, clonidine produces side effects such as sedation, mouth dry, and depression. Moxonidine and rilmenidine, compounds of the second generation of imidazoline drugs, with fewer side effects, display a higher affinity for the imidazoline receptors compared with α2-adrenoceptors. The antihypertensive action of these drugs is due to inhibition of the sympathetic outflow primarily through central I1-imidazoline receptors in the RVLM, although others anatomical sites and mechanisms/receptors are involved. Agmatine is regarded as the endogenous ligand for imidazoline receptors. This amine modulates the cardiovascular function. Indeed, when administered in the RVLM mimics the hypotension of clonidine. Results: Recent findings have shown that imidazoline drugs also exert biological response directly on the cardiovascular tissues, which can contribute to their antihypertensive response. Currently, new imidazoline receptors ligands are in development. Conclusion: In the present review, we provide a brief update on the cardiovascular effects of clonidine, moxonidine, rilmenidine, and the novel imidazoline agents since representing an important therapeutic target for some cardiovascular diseases.

2021 ◽  
Author(s):  
Fabrice Cognasse ◽  
Kathryn Hally ◽  
Sebastien Fauteux-Daniel ◽  
Marie-Ange Eyraud ◽  
Charles-Antoine Arthaud ◽  
...  

AbstractAside from their canonical role in hemostasis, it is increasingly recognized that platelets have inflammatory functions and can regulate both adaptive and innate immune responses. The main topic this review aims to cover is the proinflammatory effects and side effects of platelet transfusion. Platelets prepared for transfusion are subject to stress injury upon collection, preparation, and storage. With these types of stress, they undergo morphologic, metabolic, and functional modulations which are likely to induce platelet activation and the release of biological response modifiers (BRMs). As a consequence, platelet concentrates (PCs) accumulate BRMs during processing and storage, and these BRMs are ultimately transfused alongside platelets. It has been shown that BRMs present in PCs can induce immune responses and posttransfusion reactions in the transfusion recipient. Several recent reports within the transfusion literature have investigated the concept of platelets as immune cells. Nevertheless, current and future investigations will face the challenge of encompassing the immunological role of platelets in the scope of transfusion.


Author(s):  
Samuel Baek ◽  
Seok Kim ◽  
Myung Ho Shin ◽  
Tae Min Kim ◽  
Seoung-Joon Lee ◽  
...  

Purpose: We introduce the novel treatment technique, scalene injection, and study its clinical efficacy for diagnosis, treatment, and pain control for patients with thoracic outlet syndrome.Methods: Between November 2001 and October 2018, 266 patients were studied retrospectively. To evaluate the efficacy and sustainability, we checked the numerical rating scale (NRS) for pain relief and neck disability index (NDI) for functional improvements, prior to and 1, 12 weeks after the injection. The safety was evaluated by examining side effects for at least 24 hours from the point of injection.Results: NRS was improved from 7.12 to 3.11 at 1 week, and to 3.05 at 12 weeks (p<0.05). NDI was improved from 15.87 to 6.15 at 1 week, and to 6.19 at 12 weeks (p<0.05). There were two cases of convulsion immediately after the injection and were treated with prompt oxygen supply and sedatives. Transient side effects included two cases of dyspnea and one case of nausea and were resolved within 1 hour after. All five cases showed symptoms of side effects on the day of injection and were resolved within a day. A total of 242 patients (91.0%) experienced immediate declines in NRS and 161 patients experienced persistent declines for more than 12 weeks. However, 24 patients (9.0%) showed no improvement and 20 patients (7.5%) experienced increases in NRS.Conclusion: Scalene injection is also effective as a therapeutic method. However, this study suggests that it must be done with monitoring of vital signs in an operating room for any possible complications and side effects.


2008 ◽  
Vol 86 (11) ◽  
pp. 804-814 ◽  
Author(s):  
Daniela Mokra ◽  
Ingrid Tonhajzerova ◽  
Juraj Mokry ◽  
Anna Drgova ◽  
Maria Petraskova ◽  
...  

Glucocorticoids may improve lung function in newborns with meconium aspiration syndrome (MAS), but information on the acute side effects of glucocorticoids in infants is limited. In this study using a rabbit model of MAS, we addressed the hypothesis that systemic administration of dexamethasone causes acute cardiovascular changes. Adult rabbits were treated with 2 intravenous doses of dexamethasone (0.5 mg/kg each) or saline at 0.5 h and 2.5 h after intratracheal instillation of human meconium or saline. Animals were oxygen-ventilated for 5 h after the first dose of treatment. Blood pressure, heart rate, and short-term heart rate variability (HRV) were analyzed during treatment, for 5 min immediately after each dose, and for the 5 h of the experiment. In the meconium-instilled animals, dexamethasone increased blood pressure, decreased heart rate, increased HRV parameters, and caused cardiac arrhythmia during and immediately after administration. In the saline-instilled animals, the effect of dexamethasone was inconsistent. In these animals, the acute effects of dexamethasone on blood pressure and cardiac rhythm were reversed after 30 min, whereas heart rate continued to decrease and HRV parameters continued to increase for 5 h after the first dose of dexamethasone. These effects were more pronounced in meconium-instilled animals. If systemic glucocorticoids are used in the treatment of MAS, cardiovascular side effects of glucocorticoids should be considered.


2018 ◽  
Vol 235 (7) ◽  
pp. 1955-1965 ◽  
Author(s):  
Valentina Vengeliene ◽  
Tatiane T. Takahashi ◽  
Olga A. Dravolina ◽  
Irina Belozertseva ◽  
Edwin Zvartau ◽  
...  

2021 ◽  
Author(s):  
Moataz Dowaidar

It is possible to understand both the processes of ferroptosis and how this type of cell death will be harnessed in the near future. The novel ferroposis-based therapies will also be created and evaluated using various biomarkers. Selenium and vitamin E have been shown to support some types of cancer in several studies. Such environmental factors should be accounted for while exploring ferroaptosis's duties. The effect of these modifications will be dictated by the cellular and environmental context in which they are created. It is critical to determine whether the inhibitor can act as a lipophilic radical-trapping antioxidant and prevent ferroPTosis independently of the enzyme under investigation, as several studies with lipoxygenases have shown.Using pharmacological approaches to evaluate ferropsosis can have potential side effects that are difficult to measure. Using small-molecule probes may be investigated using small-molecules probes. It's essential to utilize a biochemical test or a pharmacodynamic marker of target inhibition when employing RSL3 to inhibit GPX4, or when using erastin to inhibit the system xc–cystine/glutamate antiporter, or by using an Xc–Cystine/Glutamate/Glutamic antiporter inhibitor, or an erast inhibitor, to inhibit Gpx4, GSH, and other types of protein thiols, such as GSH and protein thiola. Many tiny molecules that are potent and selective probes in cellular assays have limited applicability in animal studies. RSL3, a poor solubility, is useful only in instances when an injection is made directly into tissues or tumors. Interfering with iron to modulate ferroptosis has far-reaching ramifications. Findings obtained with iron chelators only should be interpreted with caution as depleting iron can have other side effects other than ferroPTosis suppression.


Author(s):  
Josef Niebauer ◽  
Carl Johan Sundberg

The abuse of doping substances is prevalent in sports and in society at large. Doping substances are also present in a substantial fraction of nutritional supplements. They can cause severe side effects. This chapter is focused on cardiovascular side effects. Androgenic anabolic steroids can induce left ventricular hypertrophy, heart fibrosis, and systolic and diastolic dysfunction, and has been associated with dyslipidaemia, endothelial dysfunction, and coronary artery disease. Beta-2 agonists can induce chronotropic and inotropic effects, QT prolongation, palpitations, arrhythmias and sudden cardiac death. Erythropoietin can induce hypertension and embolism. Use of banned substances and methods in sports, i.e. doping, is prohibited, unethical, and dangerous. Research efforts in sports sciences and sports medicine are needed to prevent and treat doping abuse and to help athletes be successful without the need for doping.


1998 ◽  
Vol 275 (5) ◽  
pp. H1826-H1833 ◽  
Author(s):  
L. G. Melo ◽  
A. T. Veress ◽  
U. Ackermann ◽  
H. Sonnenberg

Atrial natriuretic peptide (ANP) exerts a chronic hypotensive effect due to a decrease in total peripheral resistance (TPR). This study examines if chronic ANP-dependent vasodilation is attributable to differences in the cardiovascular regulatory activity of vascular endothelium (VE), based on evidence that ANP affects synthesis/release and target cardiovascular effects of endothelin-1 (ET-1), C-type natriuretic peptide (CNP), and nitric oxide (NO). To determine if the synthetic activity of resistance vasculature VE is chronically altered by plasma ANP activity, we measured ET-1, CNP, and endothelial constitutive NO synthase (ecNOS) concentration and total NOS enzyme activity in homogenates of kidney, heart, lung, hindquarter skeletal muscle, and brain from hypotensive transgenic mice with elevated plasma ANP, hypertensive knockout mice (−/−) characterized by the absence of ANP, and the corresponding normotensive wild-type (NT, +/+) mice. Tissue distribution and abundance patterns of ET-1, CNP, ecNOS, and NOS enzyme activity were comparable between the different genotypes and did not differ significantly between mutant and control mice. Antagonism of ETA/B receptors in −/− and +/+ mice in vivo with SB-209670 reduced arterial blood pressure (ABP) significantly and comparably in both genotypes (−27 ± 4 and −25 ± 2% change for −/− and +/+ mice, respectively) independent of any significant changes in heart rate (HR) (−6 ± 8 and −4 ± 4% change for −/− and +/+ mice, respectively). Immunoneutralization of CNP-specific guanylate cyclase-linked receptors (GC-B) with monoclonal antibodies (3G12) increased ABP slightly, but not significantly, by similar relative amounts in both −/− (10 ± 6% change) and +/+ mice (8 ± 3% change), without changing HR significantly (4 ± 1% change for both +/+ and −/− mice). Inhibition of NOS activity (by N G-nitro-l-arginine methyl ester) significantly increased ABP, but the changes were comparable between −/− (53 ± 5% change) and +/+ mice (50 ± 6% change) and occurred in the absence of significant changes in HR (−1 ± 5 and 7 ± 5% change for −/− and +/+ mice, respectively). We conclude that the differences in ABP associated with chronic variations in endogenous ANP activity are not due to alterations in synthesis or responsiveness of the cardiovascular system to the effects of ET-1, CNP, or NO.


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