-
Brazilian Journal of Medical and... 2024Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced...
Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced arthritis (AIA), around the 15th day post-induction. Therefore, the present study aimed to verify the effects of AIA on hyporesponsiveness to phenylephrine in rat aortas. AIA was induced by intradermal injection of Mycobacterium tuberculosis (3.8 mg/dL) in the right hind paw of male Wistar rats (n=27). Functional experiments in isolated aortas were carried out 15 days after AIA induction. Morphometric and stereological analyses of the aortas were also performed 36 days after the induction of AIA. AIA did not promote structural modifications in the aortas at any of the time points studied. AIA reduced phenylephrine-induced contraction in endothelium-intact aortas, but not in endothelium-denuded aortas. However, AIA did not change KCl-induced contraction in either endothelium-intact or denuded aortas. L-NAME (non-selective NOS inhibitor), 1400W (selective iNOS inhibitor), and ODQ (guanylyl cyclase inhibitor) reversed AIA-induced hyporesponsiveness to phenylephrine in intact aortas. 7-NI (selective nNOS inhibitor) increased the contraction induced by phenylephrine in aortas from AIA rats. In summary, the hyporesponsiveness to phenylephrine induced by AIA was endothelium-dependent and mediated by iNOS-derived NO through activation of the NO-guanylyl cyclase pathway.
Topics: Animals; Male; Phenylephrine; Rats, Wistar; Arthritis, Experimental; Nitric Oxide; Vasoconstriction; Endothelium, Vascular; Vasoconstrictor Agents; Rats; Aorta
PubMed: 38775546
DOI: 10.1590/1414-431X2024e13304 -
Journal of Veterinary Internal Medicine May 2024Pulmonary hypertension (PH) in dogs with myxomatous mitral valve disease (MMVD) is caused by increased pulmonary venous pressure. Thrombosis, vascular remodeling, and...
BACKGROUND
Pulmonary hypertension (PH) in dogs with myxomatous mitral valve disease (MMVD) is caused by increased pulmonary venous pressure. Thrombosis, vascular remodeling, and vasoconstriction mediated by platelets could exacerbate PH.
HYPOTHESIS
Dogs with PH will exhibit a hypercoagulable state, characterized by increased platelet activation, platelet-leukocyte, and platelet-neutrophil aggregate formation.
ANIMALS
Eleven dogs (≥3.5 kg) diagnosed with MMVD and PH and 10 dogs with MMVD lacking PH.
METHODS
Prospective cohort ex vivo study. All dogs underwent echocardiographic examination, CBC, 3-view thoracic radiographs, and heartworm antigen testing. Severity of PH and MMVD were assessed by echocardiography. Viscoelastic monitoring of coagulation was assessed using thromboelastography (TEG). Platelet activation and platelet-leukocyte/platelet-neutrophil interactions were assessed using flow cytometry. Plasma serotonin concentrations were measured by ELISA.
RESULTS
Unstimulated platelets from dogs with MMVD and PH expressed more surface P-selectin than MMVD controls (P = .03). Platelets from dogs with MMVD and PH had persistent activation in response to agonists. The number of platelet-leukocyte aggregates was higher in dogs with MMVD and PH compared with MMVD controls (P = .01). Ex vivo stimulation of whole blood resulted in higher numbers of platelet-neutrophil aggregates in dogs with MMVD and PH (P = .01). Assessment of hypercoagulability based on TEG or plasma serotonin concentrations did not differ between groups.
CONCLUSION AND CLINICAL IMPORTANCE
Platelet hyperresponsiveness and increased platelet-neutrophil interaction occur in dogs with MMVD and PH, suggesting that platelets play a role of in the pathogenesis of PH. Clinical benefits of antiplatelet drugs in dogs with MMVD and PH require further investigation.
PubMed: 38773707
DOI: 10.1111/jvim.17067 -
Acta Pharmacologica Sinica May 2024The endothelium, lining the inner surface of blood vessels and spanning approximately 3 m, serves as the largest organ in the body. Comprised of endothelial cells, the...
The endothelium, lining the inner surface of blood vessels and spanning approximately 3 m, serves as the largest organ in the body. Comprised of endothelial cells, the endothelium interacts with other bodily components including the bloodstream, circulating cells, and the lymphatic system. Functionally, the endothelium primarily synchronizes vascular tone (by balancing vasodilation and vasoconstriction) and prevents vascular inflammation and pathologies. Consequently, endothelial dysfunction disrupts vascular homeostasis, leading to vascular injuries and diseases such as cardiovascular, cerebral, and metabolic diseases. In this opinion/perspective piece, we explore the recently identified mechanisms of endothelial dysfunction across various disease subsets and critically evaluate the strengths and limitations of current therapeutic interventions at the pre-clinical level.
PubMed: 38773228
DOI: 10.1038/s41401-024-01295-8 -
European Journal of Internal Medicine May 2024
PubMed: 38772829
DOI: 10.1016/j.ejim.2024.05.021 -
Archivos Argentinos de Pediatria May 2024Raynaud's phenomenon consists of excessive contraction of the blood vessels in response to various stimuli; although it usually affects the extremities, other locations...
Raynaud's phenomenon consists of excessive contraction of the blood vessels in response to various stimuli; although it usually affects the extremities, other locations are less frequently involved. This study focused on describing the characteristics of a series of women with Raynaud's phenomenon of the nipple. Through medical record review and direct communication with patients, data from 12 women diagnosed with Raynaud's phenomenon of the nipple between 2016 and 2023 were collected and analyzed. The following variables were assessed: age, symptoms, triggering factors, treatment, and duration of symptoms. In this case series, Raynaud's phenomenon of the nipple in breastfeeding women was more common among primiparous women around 10 days after delivery; pain was severe and, in most cases, improved with local and/or drug treatment, and did not limit the duration of breastfeeding.
PubMed: 38771559
DOI: 10.5546/aap.2023-10280.eng -
Revista Brasileira de Ginecologia E... 2024Potassium channels have an important role in the vascular adaptation during pregnancy and a reduction in the expression of adenosine triphosphate-sensitive potassium...
OBJECTIVE
Potassium channels have an important role in the vascular adaptation during pregnancy and a reduction in the expression of adenosine triphosphate-sensitive potassium channels (Katp) has been linked to preeclampsia. Activation of Katp induces vasodilation; however, no previous study has been conducted to evaluate the effects of the inhibition of these channels in the contractility of preeclamptic arteries. Glibenclamide is an oral antihyperglycemic agent that inhibits Katp and has been widely used in vascular studies.
METHODS
To investigate the effects of the inhibition of K, umbilical arteries of preeclamptic women and women with healthy pregnancies were assessed by vascular contractility experiments, in the presence or absence of glibenclamide. The umbilical arteries were challenged with cumulative concentrations of potassium chloride (KCl) and serotonin.
RESULTS
There were no differences between the groups concerning the maternal age and gestational age of the patients. The percentage of smokers, caucasians and primiparae per group was also similar. On the other hand, blood pressure parameters were elevated in the preeclamptic group. In addition, the preeclamptic group presented a significantly higher body mass index. The newborns of both groups presented similar APGAR scores and weights.
CONCLUSION
In the presence of glibenclamide, there was an increase in the KCl-induced contractions only in vessels from the PE group, showing a possible involvement of these channels in the disorder.
Topics: Humans; Female; Pregnancy; Pre-Eclampsia; Umbilical Arteries; Adult; Glyburide; Vasoconstriction; Young Adult; KATP Channels; Potassium Chloride
PubMed: 38765503
DOI: 10.61622/rbgo/2024AO02 -
Vascular Pharmacology Jun 2024Pulmonary hypertension (PH) is a progressive, severe and to date not curable disease of the pulmonary vasculature. Alterations of the insulin-like growth factor 1...
Pulmonary hypertension (PH) is a progressive, severe and to date not curable disease of the pulmonary vasculature. Alterations of the insulin-like growth factor 1 (IGF-1) system are known to play a role in vascular pathologies and IGF-binding proteins (IGFBPs) are important regulators of the bioavailability and function of IGFs. In this study, we show that circulating plasma levels of IGFBP-1, IGFBP-2 and IGFBP-3 are increased in idiopathic pulmonary arterial hypertension (IPAH) patients compared to healthy individuals. These binding proteins inhibit the IGF-1 induced IGF-1 receptor (IGF1R) phosphorylation and exhibit diverging effects on the IGF-1 induced signaling pathways in human pulmonary arterial cells (i.e. healthy as well as IPAH-hPASMCs, and healthy hPAECs). Furthermore, IGFBPs are differentially expressed in an experimental mouse model of PH. In hypoxic mouse lungs, IGFBP-1 mRNA expression is decreased whereas the mRNA for IGFBP-2 is increased. In contrast to IGFBP-1, IGFBP-2 shows vaso-constrictive properties in the murine pulmonary vasculature. Our analyses show that IGFBP-1 and IGFBP-2 exhibit diverging effects on IGF-1 signaling and display a unique IGF1R-independent kinase activation pattern in human pulmonary arterial smooth muscle cells (hPASMCs), which represent a major contributor of PAH pathobiology. Furthermore, we could show that IGFBP-2, in contrast to IGFBP-1, induces epidermal growth factor receptor (EGFR) signaling, Stat-3 activation and expression of Stat-3 target genes. Based on our results, we conclude that the IGFBP family, especially IGFBP-1, IGFBP-2 and IGFBP-3, are deregulated in PAH, that they affect IGF signaling and thereby regulate the cellular phenotype in PH.
Topics: Humans; Animals; Receptor, IGF Type 1; Signal Transduction; Pulmonary Artery; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor I; Myocytes, Smooth Muscle; Cells, Cultured; Male; Insulin-Like Growth Factor Binding Protein 1; Phosphorylation; Disease Models, Animal; STAT3 Transcription Factor; Case-Control Studies; Mice, Inbred C57BL; Familial Primary Pulmonary Hypertension; Female; ErbB Receptors; Middle Aged; Vascular Remodeling; Adult; Muscle, Smooth, Vascular
PubMed: 38762131
DOI: 10.1016/j.vph.2024.107379 -
Journal of the American Academy of... May 2024With an increase in number of patients on antithrombotic therapies, management of bleeding during dermatologic surgery is increasingly important. As described in Part 1,... (Review)
Review
With an increase in number of patients on antithrombotic therapies, management of bleeding during dermatologic surgery is increasingly important. As described in Part 1, perioperative discontinuation of antithrombotic therapies may increase the risk of embolic events thus the risks and benefits must be weighed carefully when deciding whether to continue or suspend therapy. However, continuing oral anticoagulants may result in increased intraoperative and postoperative bleeding. Here we describe various methods to effectively achieve hemostasis which include: 1) mechanical methods to compress the vasculature 2) pharmacologic agents that induce vasoconstriction 3) physiologic agents that augment clot formation and 4) physical agents that promote platelet aggregation.
PubMed: 38750938
DOI: 10.1016/j.jaad.2024.01.097 -
JACC. Cardiovascular Interventions May 2024
Topics: Humans; Coronary Artery Disease; Coronary Vessels; Treatment Outcome; Percutaneous Coronary Intervention; Vasoconstriction
PubMed: 38749598
DOI: 10.1016/j.jcin.2024.03.019 -
JACC. Cardiovascular Interventions May 2024Invasive CFT is the gold standard for diagnosing coronary vasomotor dysfunction in patients with ANOCA. Most institutions recommend only testing the left coronary... (Comparative Study)
Comparative Study
BACKGROUND
Invasive CFT is the gold standard for diagnosing coronary vasomotor dysfunction in patients with ANOCA. Most institutions recommend only testing the left coronary circulation. Therefore, it is unknown whether testing multiple coronary territories would increase diagnostic yield.
OBJECTIVES
The aim of this study was to evaluate the diagnostic yield of multivessel, compared with single-vessel, invasive coronary function testing (CFT) in patients with angina and nonobstructive coronary arteries (ANOCA).
METHODS
Multivessel CFT was systematically performed in patients with suspected ANOCA. Vasoreactivity testing was performed using acetylcholine provocation in the left (20 to 200 μg) and right (20 to 80μg) coronary arteries. A pressure-temperature sensor guidewire was used for coronary physiology assessment in all three epicardial vessels.
RESULTS
This multicenter study included a total of 228 vessels from 80 patients (57.8 ± 11.8 years of age, 60% women). Compared with single-vessel CFT, multivessel testing resulted in more patients diagnosed with coronary vasomotor dysfunction (86.3% vs 68.8%; P = 0.0005), coronary artery spasm (60.0% vs 47.5%; P = 0.004), and CMD (62.5% vs 36.3%; P < 0.001). Coronary artery spasm (n = 48) predominated in the left coronary system (n = 38), though isolated right coronary spasm was noted in 20.8% (n = 10). Coronary microvascular dysfunction (CMD), defined by abnormal index of microcirculatory resistance and/or coronary flow reserve, was present 62.5% of the cohort (n = 50). Among the cohort with CMD, 27 patients (33.8%) had 1-vessel CMD, 15 patients (18.8%) had 2-vessel CMD, and 8 patients (10%) had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major coronary vessels (left anterior descending coronary artery = 36.3%, left circumflex coronary artery = 33.8%, right coronary artery = 31.3%; P = 0.486).
CONCLUSIONS
Multivessel CFT resulted in an increased diagnostic yield in patients with ANOCA compared with single-vessel testing. The results of this study suggest that multivessel CFT has a role in the management of patients with ANOCA.
Topics: Humans; Female; Male; Middle Aged; Aged; Predictive Value of Tests; Coronary Vessels; Vasodilator Agents; Coronary Vasospasm; Acetylcholine; Coronary Circulation; Angina Pectoris; Coronary Artery Disease; Cardiac Catheterization; Coronary Angiography; Reproducibility of Results; Vasodilation; Vasoconstriction
PubMed: 38749588
DOI: 10.1016/j.jcin.2024.03.007