scholarly journals Increased endothelin-1 production in diabetic patients after cardioplegic arrest and reperfusion impairs coronary vascular reactivity: Reversal by means of endothelin antagonism

2002 ◽  
Vol 123 (6) ◽  
pp. 1114-1119 ◽  
Author(s):  
Subodh Verma ◽  
Andrew Maitland ◽  
Richard D. Weisel ◽  
Paul W.M. Fedak ◽  
Shu-Hong Li ◽  
...  
Keyword(s):  
Vascular Reactivity ◽  
Diabetic Patients ◽  
Cardioplegic Arrest ◽  
Endothelin 1

Metabolic and endothelial effects of trimetazidine on forearm skeletal muscle in patients with type 2 diabetes and ischemic cardiomyopathy

2006 ◽  
Vol 290 (1) ◽  
pp. E54-E59 ◽  
Author(s):  
Lucilla D. Monti ◽  
Emanuela Setola ◽  
Gabriele Fragasso ◽  
Riccardo P. Camisasca ◽  
Pietro Lucotti ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Lipid Oxidation ◽  
Ischemic Cardiomyopathy ◽  
Glucose Oxidation ◽  
Diabetic Patients ◽  
Vascular Effects ◽  
Type 2 Diabetic Patients ◽  
Double Blind ◽  
Endothelin 1

The aim of the present study was to evaluate the effect of prolonged inhibition of β-oxidation on glucose and lipid muscle forearm metabolism and cGMP and endothelin-1 forearm release in patients with type 2 diabetes mellitus and ischemic cardiomyopathy. Fifteen patients were randomly allocated in a double-blind cross-over parallel study with trimetazidine (20 mg tid) or placebo lasting 15 days. At the end of each period, all patients underwent euglycemic hyperinsulinemic clamps with forearm indirect calorimetry and endothelial balance of vasodilator and vasoconstricor factors. Compared with placebo, trimetazidine induced 1) an increase in insulin-induced forearm glucose uptake and glucose oxidation accompained by a reduction in forearm lipid oxidation and citrate release and 2) a decrease of endothelin-1 release paralleled by a significant increase in forearm cGMP release. Forearm glucose oxidation significantly correlated with cGMP release ( r = 0.37, P < 0.04), whereas forearm lipid oxidation positively correlated with endothelin-1 release ( r = 0.40, P < 0.03). In conclusion, for the first time, we demonstrated that insulin-induced forearm glucose oxidation and forearm cGMP release were increased whereas forearm endothelin-1 release was decreased during trimetazidine treatment. Muscle's metabolic and vascular effects of trimetazidine add new interest in the use of trimetazidine in type 2 diabetic patients with cardiovascular disease.

Endothelin-1 during reperfusion of the human heart after cardioplegic arrest

1994 ◽  
Vol 8 (5) ◽  
pp. 59
Author(s):  
P. Mair ◽  
D. Balogh ◽  
J. Bleier ◽  
W. Furtwaengler ◽  
R. German ◽  
...  
Keyword(s):  
Human Heart ◽  
Cardioplegic Arrest ◽  
Endothelin 1

Endothelin-1 and pancreatic islet vasculature: studies in vivo and on isolated, vascularly perfused pancreatic islets

2007 ◽  
Vol 292 (6) ◽  
pp. E1616-E1623 ◽  
Author(s):  
En Yin Lai ◽  
A. Erik G. Persson ◽  
Birgitta Bodin ◽  
Örjan Källskog ◽  
Arne Andersson ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pancreatic Islet ◽  
Vascular Reactivity ◽  
Blood Perfusion ◽  
Receptor Subtype ◽  
Endothelin 1 ◽  
Islet Blood Flow ◽  
Endothelin B

Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor, which also stimulates insulin release. The aim of the present study was to evaluate whether exogenously administered ET-1 affected pancreatic islet blood flow in vivo in rats and the islet arteriolar reactivity in vitro in mice. Furthermore, we aimed to determine the ET-receptor subtype that was involved in such responses. When applying a microsphere technique for measurements of islet blood perfusion in vivo, we found that ET-1 (5 nmol/kg) consistently and markedly decreased total pancreatic and especially islet blood flow, despite having only minor effects on blood pressure. Neither endothelin A (ETA) receptor (BQ-123) nor endothelin-B (ETB) receptor (BQ-788) antagonists, alone or in combination, could prevent this reduction in blood flow. To avoid confounding interactions in vivo, we also examined the arteriolar vascular reactivity in isolated, perfused mouse islets. In the latter preparation, we demonstrated a dose-dependent constriction in response to ET-1. Administration of BQ-123 prevented this, whereas BQ-788 induced a right shift in the response. In conclusion, the pancreatic islet vasculature is highly sensitive to exogenous ET-1, which mediates its effect mainly through ETA receptors.

Cholesterol Modulates Vascular Reactivity to Endothelin-1 by Stimulating a Pro-inflammatory Pathway

2000 ◽  
Vol 274 (2) ◽  
pp. 553-558 ◽  
Author(s):  
Daniel Paris ◽  
Terrence Town ◽  
James Humphrey ◽  
Kiyoko Yokota ◽  
Michael Mullan
Keyword(s):  
Vascular Reactivity ◽  
Inflammatory Pathway ◽  
Endothelin 1

scholarly journals VE-PTP inhibition elicits eNOS phosphorylation to blunt endothelial dysfunction and hypertension in diabetes

2020 ◽  
Author(s):  
Mauro Siragusa ◽  
Alberto Fernando Oliveira Justo ◽  
Pedro Felipe Malacarne ◽  
Anna Strano ◽  
Akshay Buch ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Dysfunction ◽  
Vascular Reactivity ◽  
Therapeutic Option ◽  
Diabetic Patients ◽  
No Production ◽  
Vascular Endothelial ◽  
Enos Activity

Abstract Aims Receptor-type vascular endothelial protein tyrosine phosphatase (VE-PTP) dephosphorylates Tie-2 as well as CD31, VE-cadherin, and vascular endothelial growth factor receptor 2 (VEGFR2). The latter form a signal transduction complex that mediates the endothelial cell response to shear stress, including the activation of the endothelial nitric oxide (NO) synthase (eNOS). As VE-PTP expression is increased in diabetes, we investigated the consequences of VE-PTP inhibition (using AKB-9778) on blood pressure in diabetic patients and the role of VE-PTP in the regulation of eNOS activity and vascular reactivity. Methods and results In diabetic patients AKB-9778 significantly lowered systolic and diastolic blood pressure. This could be linked to elevated NO production, as AKB increased NO generation by cultured endothelial cells and elicited the NOS inhibitor-sensitive relaxation of endothelium-intact rings of mouse aorta. At the molecular level, VE-PTP inhibition increased the phosphorylation of eNOS on Tyr81 and Ser1177 (human sequence). The PIEZO1 activator Yoda1, which was used to mimic the response to shear stress, also increased eNOS Tyr81 phosphorylation, an effect that was enhanced by VE-PTP inhibition. Two kinases, i.e. abelson-tyrosine protein kinase (ABL)1 and Src were identified as eNOS Tyr81 kinases as their inhibition and down-regulation significantly reduced the basal and Yoda1-induced tyrosine phosphorylation and activity of eNOS. VE-PTP, on the other hand, formed a complex with eNOS in endothelial cells and directly dephosphorylated eNOS Tyr81 in vitro. Finally, phosphorylation of eNOS on Tyr80 (murine sequence) was found to be reduced in diabetic mice and diabetes-induced endothelial dysfunction (isolated aortic rings) was blunted by VE-PTP inhibition. Conclusions VE-PTP inhibition enhances eNOS activity to improve endothelial function and decrease blood pressure indirectly, through the activation of Tie-2 and the CD31/VE-cadherin/VEGFR2 complex, and directly by dephosphorylating eNOS Tyr81. VE-PTP inhibition, therefore, represents an attractive novel therapeutic option for diabetes-induced endothelial dysfunction and hypertension.

Evidence for NO involvement in regulating vascular reactivity in balloon-injured rat carotid artery

1995 ◽  
Vol 269 (3) ◽  
pp. H988-H996 ◽  
Author(s):  
T. C. Major ◽  
R. W. Overhiser ◽  
R. L. Panek
Keyword(s):  
Carotid Artery ◽  
Factor Viii ◽  
Vascular Reactivity ◽  
Carotid Arteries ◽  
Muscarinic Agonist ◽  
Ang Ii ◽  
Histomorphometric Analysis ◽  
Balloon Injury ◽  
Contractile Responses ◽  
Endothelin 1

The present study evaluated the influence of this newly formed intima on vascular reactivity in balloon-injured carotid arteries and the regulatory role of the vasodilator, nitric oxide (NO). Balloon injury was performed using a 2-F Fogarty catheter. After 2 and 4 wk, carotid artery segments were removed for both histomorphometric analysis and determination of in vitro contractile responses. Histomorphometric analysis showed a marked intimal thickening with an intima-to-media ratio of 126 +/- 19% (n = 5). The lack of factor VIII staining in injured carotid arteries revealed the absence of endothelium, since factor VIII-related antigen is a glycoprotein synthesized by endothelial cells. Functionally, maximal contractile responses to norepinephrine, angiotensin II (ANG II), endothelin-1, and serotonin were all attenuated in the injured vessels compared with the uninjured carotid arteries [0.38 +/- 0.11 vs. 0.73 +/- 0.10 g (n = 5), norepinephrine; 0.15 +/- 0.06 vs. 0.38 +/- 0.05 g (n = 4), ANG II; 0.60 +/- 0.14 vs. 1.05 +/- 0.12 g (n = 4), endothelin-1; 0.23 +/- 0.07 vs. 0.60 +/- 0.06 g (n = 12), serotonin]. Contractile responses induced by KCl were not affected by the balloon injury (0.62 +/- 0.10 vs. 0.64 +/- 0.09 g, n = 4). Interestingly, carbachol, a muscarinic agonist and vasodilator, caused concentration-dependent relaxations in 2- as well as 4-wk postinjured vessels despite the absence of endothelium. The NO synthase inhibitors, N omega-L-arginine methyl ester (L-NAME) and N omega-nitro-L-arginine (L-NNA), blocked the relaxation responses evoked by carbachol. Exogenously administered L-arginine reversed this blockade of the NOS inhibitors on the carbachol-induced relaxations. In addition, L-NAME partially reversed in a concentration-dependent manner the reduced maximal contractile force elicited by serotonin in the injured carotid artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of lysophosphatidic acid in endothelin-1- and hematoma-induced alteration of cerebral microcirculation

1997 ◽  
Vol 273 (2) ◽  
pp. R703-R709 ◽  
Author(s):  
M. A. Yakubu ◽  
K. Liliom ◽  
G. J. Tigyi ◽  
C. W. Leffler
Keyword(s):  
Lysophosphatidic Acid ◽  
Vascular Reactivity ◽  
Intrathecal Injection ◽  
Brain Parenchyma ◽  
Cerebrovascular Reactivity ◽  
Lipid Mediator ◽  
Endothelin 1 ◽  
Potential Contributor ◽  
Cerebral Hematoma ◽  
Left Parietal Cortex

Cerebral hematoma increases cerebrospinal fluid (CSF) endothelin-1 (ET-1). Inhibitors of ET-1 synthesis prevent this increment and hematoma-induced modification of cerebral arteriolar reactivity. We hypothesized that intrathecal ET-1 injection could 1) modify pial arteriolar reactivity similarly to hematoma; 2) increase CSF lysophosphatidic acid (LPA), a potential contributor to altered cerebrovascular reactivity; and 3) reduce the level of adenosine 3',5'-cyclic monophosphate (cAMP) in the CSF. Either ET-1 (10(-7) M) or artificial CSF was injected over the left parietal cortex of newborn pigs. Four days later, cranial windows were implanted. CSF ET was increased from a basal level of 11 fmol/ml to 18 fmol/ml 4 days after ET-1 injection, whereas CSF cAMP was reduced from 2,700 to 950 fmol/ml. The mean diameter of pial arterioles was reduced 31%. In control animals, 10(-12) M ET caused dilation, and higher concentrations induced vasoconstriction. Four days after ET-1 injection topical ET-1 caused constriction instead of dilation at 10(-12) M, and constrictions at higher doses were enhanced. Norepinephrine-induced constrictions were potentiated in the ET-1-injected group. Dilations to cAMP-dependent (but not independent) vasodilators were attenuated after ET-1. The concentration of the vasoconstrictor lipid mediator LPA increased approximately fourfold. Thus intrathecal injection of ET-1 mimics hematoma-induced modification of cerebral vascular reactivity and increase in LPA production. The mechanism(s) of ET-1- and hematoma-induced modifications may involve LPA, which is known to contribute to the loss of dilator responses by inhibition of cAMP product on. The present study further suggests that ET-1 together with LPA could be causing changes in cerebrovascular reactivity following cerebral hemorrhage. ET-1 stimulates the release of LPA from brain parenchyma independent of serum so that LPA could serve as a secondary mediator.

scholarly journals Impaired coronary contraction to phenylephrine after cardioplegic arrest in diabetic patients

2018 ◽  
Vol 230 ◽  
pp. 80-86 ◽  
Author(s):  
Nicholas Sellke ◽  
Caroline Gordon ◽  
Isabella Lawandy ◽  
Anastassia Y. Gorvitovskaia ◽  
Laura A. Scrimgeour ◽  
...  
Keyword(s):  
Diabetic Patients ◽  
Cardioplegic Arrest

Decreased Contractile Response to Endothelin-1 of Peripheral Microvasculature from Diabetic Patients

2010 ◽  
Vol 158 (2) ◽  
pp. 226-227
Author(s):  
J. Feng ◽  
Y. Liu ◽  
K.R. Khabbaz ◽  
R. Hagberg ◽  
M. Robich ◽  
...  
Keyword(s):  
Contractile Response ◽  
Diabetic Patients ◽  
Endothelin 1
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