scholarly journals Microcirculatory aspects of neurogenic bladder syndrome

2020 ◽  
Author(s):  
Péter Járomi
Keyword(s):  
Endothelial Cell ◽  
Urinary Bladder ◽  
Disease Severity ◽  
Neurogenic Bladder ◽  
Transient Receptor Potential ◽  
Ischemia Reperfusion ◽  
Hemorrhagic Cystitis ◽  
Endothelial Damage ◽  
Transient Receptor Potential Vanilloid ◽  
Leukocyte Rolling

The microcirculatory aspects of inflammatory disorders are of importance in the pathology of the urinary system. Our first aim was to perform a comparative analysis of the microcirculatory responses of the urinary bladder in infectious and non-infectious inflammatory animal models with direct or indirect endothelial damage. To this end, we compared the local microcirculatory consequences of experimental interstitial (IC) cystitis and hemorrhagic cystitis (HC) with those of bladder ischemia/reperfusion (IR). We found that not only IR, where direct endothelial damage is present, but also HC and IC, where microcirculatory inflammatory reactions are secondary after urothelial and interstitial damage, are associated with manifest polymorphonuclear leukocyte (PMN)–endothelial cell interactions. This finding confirms the common role of PMN-mediated microcirculatory reactions in the pathogenesis of bladder diseases. The overexpression of transient receptor potential vanilloid type 1 (TRPV1) has been demonstrated in IC cases as well as in cases of neurogenic bladder. In addition, TRPV1 agonists have also previously been used during pharmacological management of these diseases. Therefore, our next aim was to examine the microcirculatory effects of local capsaicin treatment (the archetypical TRPV1 agonist). In our study, capsaicin induced rapid increases in PMN leukocyte rolling and adhesion and in adhesion molecule expression in the postcapillary venules of the urinary bladder, which was prevented by neonatal sensory chemodenervation with capsaicin and competitive TRPV1 antagonism. The effect of specific receptor antagonist therapy showed that TRPV1-induced calcitonin gene-related peptide (CGRP) release initiates the PMN–endothelial cell interaction by promoting leukocyte rolling, but adhesion is influenced by both CGRP and substance P. Our final goal is to implement medical research in clinical practice. Depending on the underlying cause, neurogenic bladder can manifest in both overactive and underactive forms. Diagnosis and treatment of both manifestations of neurogenic bladder remain a challenge in urology practice because disease severity cannot easily be assessed and the most common symptoms are non-specific. For this reason, our last aim was to provide an algorithm that aims to facilitate rapid and efficient diagnosis and assessment of disease severity. This may also aid in decision making on the potential pharmacological and invasive therapeutic approaches to protecting the upper urinary tract by maintaining low pressure values in the bladder.

Leukocyte adhesion in local versus hemorrhage-induced ischemia

1992 ◽  
Vol 263 (3) ◽  
pp. H810-H815 ◽  
Author(s):  
M. A. Perry ◽  
D. N. Granger
Keyword(s):  
Endothelial Cell ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
Leukocyte Rolling ◽  
Leukocyte Adherence ◽  
Rolling Velocity ◽  
Local Ischemia ◽  
Cell Adhesive ◽  
Local Restriction ◽  
Adhesive Interactions

The objective of this study was to compare the leukocyte-endothelial cell adhesive interactions elicited in postcapillary venules by either local ischemia-reperfusion or hemorrhage-reperfusion. Leukocyte rolling, adherence, and emigration were monitored in cat mesenteric venules exposed to an 85% reduction in blood flow (induced by either hemorrhage or local restriction of arterial inflow) for 1 h, followed by 1 h reperfusion. Leukocyte-endothelial cell interactions, venular diameter, and red blood cell velocity were measured during baseline, ischemia, and reperfusion periods. Both local and hemorrhage-induced ischemia reperfusion caused a reduction in leukocyte rolling velocity and increases in leukocyte adherence and emigration. Quantitatively, the adherence and emigration responses in both ischemia models were nearly identical. However, the two models differed in their response to immunoneutralization of the leukocyte adhesion glycoprotein CD11/CD18 with monoclonal antibody (MAb) IB4. The MAb had a more profound effect in attenuating leukocyte adherence and emigration in the local ischemia model. These results indicate that different factors may contribute to leukocyte-endothelial cell adhesive interactions observed in local vs. systemic models of ischemia-reperfusion.

scholarly journals Extracellular histones induce calcium signals in the endothelium of resistance-sized mesenteric arteries and cause loss of endothelium-dependent dilation

2019 ◽  
Vol 316 (6) ◽  
pp. H1309-H1322 ◽  
Author(s):  
Daniel M. Collier ◽  
Nuria Villalba ◽  
Adrian Sackheim ◽  
Adrian D. Bonev ◽  
Zachary D. Miller ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Transient Receptor Potential ◽  
Prolonged Exposure ◽  
Vascular Dysfunction ◽  
Receptor Potential ◽  
Mesenteric Arteries ◽  
Transient Receptor Potential Vanilloid ◽  
Histone Proteins ◽  
Genetic Ablation ◽  
Channel Inhibition

Histone proteins are elevated in the circulation after traumatic injury owing to cellular lysis and release from neutrophils. Elevated circulating histones in trauma contribute to coagulopathy and mortality through a mechanism suspected to involve endothelial cell (EC) dysfunction. However, the functional consequences of histone exposure on intact blood vessels are unknown. Here, we sought to understand the effects of clinically relevant concentrations of histones on the endothelium in intact, resistance-sized, mesenteric arteries (MAs). EC Ca2+ was measured with high spatial and temporal resolution in MAs from mice selectively expressing the EC-specific, genetically encoded ratiometric Ca2+ indicator, Cx40-GCaMP-GR, and vessel diameter was measured by edge detection. Application of purified histone protein directly to the endothelium of en face mouse and human MA preparations produced large Ca2+ signals that spread within and between ECs. Surprisingly, luminal application of histones had no effect on the diameter of pressurized arteries. Instead, after prolonged exposure (30 min), it reduced dilations to endothelium-dependent vasodilators and ultimately caused death of ~25% of ECs, as evidenced by markedly elevated cytosolic Ca2+ levels (793 ± 75 nM) and uptake of propidium iodide. Removal of extracellular Ca2+ but not depletion of intracellular Ca2+ stores prevented histone-induced Ca2+ signals. Histone-induced signals were not suppressed by transient receptor potential vanilloid 4 (TRPV4) channel inhibition (100 nM GSK2193874) or genetic ablation of TRPV4 channels or Toll-like receptor receptors. These data demonstrate that histones are robust activators of noncanonical EC Ca2+ signaling, which cause vascular dysfunction through loss of endothelium-dependent dilation in resistance-sized MAs. NEW & NOTEWORTHY We describe the first use of the endothelial cell (EC)-specific, ratiometric, genetically encoded Ca2+ indicator, Cx40-GCaMP-GR, to study the effect of histone proteins on EC Ca2+ signaling. We found that histones induce an influx of Ca2+ in ECs that does not cause vasodilation but instead causes Ca2+ overload, EC death, and vascular dysfunction in the form of lost endothelium-dependent dilation.

scholarly journals Transient Receptor Potential Vanilloid Type 1 Contributes to Modulate the Nitric Oxide Pathway and Oxidative Stress in the Isolated and Perfused Rat Heart during Ischemia and Reperfusion

2021 ◽  
Author(s):  
Vicente Castrejón-Téllez ◽  
Leonardo Del Valle-Mondragón ◽  
Israel Pérez-Torres ◽  
Verónica Guarner-Lans ◽  
Gustavo Pastelín-Hernández ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Transient Receptor Potential ◽  
Ischemia Reperfusion ◽  
Receptor Potential ◽  
Histological Evaluation ◽  
Transient Receptor Potential Vanilloid ◽  
Ischemia And Reperfusion ◽  
Cardiac Work ◽  
Western Blots

The transient vanilloid receptor potential type 1 (TRPV1) regulates neuronal and vascular functions mediated by nitric oxide (NO) and by the calcitonin gene-related peptide (CGRP). Here we study the participation of TRPV1 in the regulation of myocardial injury caused by ischemia-reperfusion and in the regulation of NO, tetrahydrobiopterin (BH4), the cGMP pathway, CGRP, total antioxidant capacity (TAC), malondialdehyde (MDA) and phosphodiesterase-3 (PDE-3). Isolated hearts of Wistar rats were used (according to Langendorff) to study the effects of capsaicin (CS), capsazepine (CZ) and CZ+CS treatments. The hearts were divided into three subgroups; 1) perfusion, 2) ischemia and 3) ischemia-reperfusion. In all groups we studied cardiac work and levels of NO, cGMP, BH4, CGRP, TAC, MDA and PDE-3 in ventricular tissue. Western blots were used to determine the expressions of eNOS, iNOS and phosphorylated NOS (pNOS). Structural changes were determined by histological evaluation. CS prevented damage caused by ischemia-reperfusion by improving cardiac work and the levels of NO, cGMP, BH4, TAC and CGRP. TRPV1 and iNOS expression were increased under ischemic conditions, while eNOS and pNOS were not modified. We conclude that the activation of TRPV1 constitutes a therapeutic possibility to counteract the damage caused by ischemia and reperfusion by regulating the NO pathway through CGRP.

scholarly journals Protective Effects of TRPV1 Activation Against Cardiac Ischemia/ Reperfusion Injury is Blunted by Diet-Induced Obesity

2020 ◽  
Vol 20 (2) ◽  
pp. 122-130
Author(s):  
Beihua Zhong ◽  
Shuangtao Ma ◽  
Donna H. Wang
Keyword(s):  
Infarct Size ◽  
Transient Receptor Potential ◽  
Diastolic Pressure ◽  
Gene Knockout ◽  
Ischemia Reperfusion ◽  
Control Diet ◽  
Left Ventricular ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channels ◽  
Postischemic Recovery

Background: Activation of Transient Receptor Potential Vanilloid Subtype 1 (TRPV1) channels protects the heart from Ischemia/Reperfusion (I/R) injury through releasing Calcitonin Gene-Related Peptide (CGRP) and Substance P (SP). The current study aimed to study the cardioprotective effects of TRPV1 in obesity. Methods: TRPV1 gene knockout (TRPV1-/-) and Wild-Type (WT) mice were Fed a High-Fat Diet (HFD) or a control diet or for 20 weeks, and then the hearts were collected for I/R injury ex vivo. The hearts were mounted on a Langendorff apparatus and subjected to ischemia (30 min) and reperfusion (40 min) after incubated with capsaicin (10 nmol/L), CGRP (0.1 μmol/L) and SP (0.1 μmol/L). Then, Coronary Flow (CF), left ventricular peak positive dP/dt (+dP/dt), Left Ventricular Developed Pressure (LVDP) and Left Ventricular End-Diastolic Pressure (LVEDP) were measured. Results: HFD intake remarkably reduced CF, +dP/dt and LVDP and elevated LVEDP in both strains (P<0.05). Treatment with capsaicin decreased infarct size, increased CF, +dP/dt and LVDP, and decreased LVEDP in WT mice on control diet (P<0.05), but did not do so in other three groups. Treatment with CGRP and SP decreased infarct size in both strains fed with control diet (P<0.05). In contrast, not all the parameters of cardiac postischemic recovery in HFD-fed WT and TRPV1-/- mice were improved by CGRP and SP. Conclusions: These results suggest that HFD intake impairs cardiac postischemic recovery. HFDinduced impairment of recovery is alleviated by CGRP in both strains and by SP only in TRPV1-/- mice, indicating that the effects of CGRP and SP are differentially regulated during HFD intake.

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