Endothelin receptor antagonism: treatment of pulmonary hypertension

2001 ◽  
Vol &NA; (1311) ◽  
pp. 9-10
Author(s):  
Anoma Ranaweera
Keyword(s):  
Pulmonary Hypertension ◽  
Endothelin Receptor ◽  
Receptor Antagonism

scholarly journals Impaired pulmonary vasomotor control in exercising swine with multiple comorbidities

2021 ◽  
Vol 116 (1) ◽  
Author(s):  
Jens van de Wouw ◽  
Jarno J. Steenhorst ◽  
Oana Sorop ◽  
Ruben W. A. van Drie ◽  
Piotr A. Wielopolski ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Vascular Resistance ◽  
Left Ventricular ◽  
Swine Model ◽  
Endothelin Receptor ◽  
Ros Scavenging ◽  
Vasomotor Control ◽  
Receptor Antagonism ◽  
Phosphodiesterase 5

AbstractPulmonary hypertension is common in heart failure with preserved ejection fraction (HFpEF). Here, we tested the hypothesis that comorbidities [diabetes mellitus (DM, streptozotocin), hypercholesterolemia (HC, high-fat diet) and chronic kidney disease (CKD, renal microembolization)] directly impair pulmonary vasomotor control in a DM + HC + CKD swine model. 6 months after induction of DM + HC + CKD, pulmonary arterial pressure was similar in chronically instrumented female DM + HC + CKD (n = 19) and Healthy swine (n = 18). However, cardiac output was lower both at rest and during exercise, implying an elevated pulmonary vascular resistance (PVR) in DM + HC + CKD swine (153 ± 10 vs. 122 ± 9 mmHg∙L−1∙min∙kg). Phosphodiesterase 5 inhibition and endothelin receptor antagonism decreased PVR in DM + HC + CKD (− 12 ± 12 and − 22 ± 7 mmHg∙L−1∙min∙kg) but not in Healthy swine (− 1 ± 12 and 2 ± 14 mmHg∙L−1∙min∙kg), indicating increased vasoconstrictor influences of phosphodiesterase 5 and endothelin. Inhibition of nitric oxide synthase produced pulmonary vasoconstriction that was similar in Healthy and DM + HC + CKD swine, but unmasked a pulmonary vasodilator effect of endothelin receptor antagonism in Healthy (− 56 ± 26 mmHg∙L−1∙min∙kg), whereas it failed to significantly decrease PVR in DM + HC + CKD, indicating loss of nitric oxide mediated inhibition of endothelin in DM + HC + CKD. Scavenging of reactive oxygen species (ROS) had no effect on PVR in either Healthy or DM + HC + CKD swine. Cardiovascular magnetic resonance imaging, under anesthesia, showed no right ventricular changes. Finally, despite an increased contribution of endogenous nitric oxide to vasomotor tone regulation in the systemic vasculature, systemic vascular resistance at rest was higher in DM + HC + CKD compared to Healthy swine (824 ± 41 vs. 698 ± 35 mmHg∙L−1∙min∙kg). ROS scavenging induced systemic vasodilation in DM + HC + CKD, but not Healthy swine. In conclusion, common comorbidities directly alter pulmonary vascular control, by enhanced PDE5 and endothelin-mediated vasoconstrictor influences, well before overt left ventricular backward failure or pulmonary hypertension develop.

scholarly journals Multidimensional fatigue in pulmonary hypertension: prevalence, severity and predictors

2018 ◽  
Vol 4 (1) ◽  
pp. 00079-2017 ◽  
Author(s):  
Todd M. Tartavoulle ◽  
Aryn C. Karpinski ◽  
Andrew Aubin ◽  
Benzi M. Kluger ◽  
Oliver Distler ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Pulmonary Hypertension ◽  
Receptor Antagonist ◽  
Body Mass ◽  
Phosphodiesterase Inhibitor ◽  
Endothelin Receptor Antagonist ◽  
Endothelin Receptor ◽  
Physical Fatigue ◽  
General Fatigue ◽  
Reduced Activity

Pulmonary hypertension is a potentially fatal disease. Despite pharmacological advances in pulmonary hypertension, fatigue remains common in patients with pulmonary hypertension.A convenience sample of 120 participants at an international patient conference completed the Multidimensional Fatigue Inventory (MFI)-20 scale. Data on New York Heart Association Functional Class, body mass index, oxygen use and medication type/use were also collected.There was a high prevalence of “severe” to “very severe” fatigue for each dimension: General Fatigue (60%), Physical Fatigue (55.8%), Reduced Activity (41.7%), Reduced Motivation (32.5%) and Mental Fatigue (27.5%). The mean±sd overall MFI-20 score was 58±5.1. Dimensions with the highest averaged levels were General Fatigue (13.40±3.61), Physical Fatigue (13.23±3.67) and Reduced Activity (11.33±4.16). Body mass index correlated with higher fatigue scores. Phosphodiesterase inhibitor plus endothelin receptor antagonist combination negatively predicted General Fatigue, Physical Fatigue, Reduced Motivation and Reduced Activity. Triple therapy was a significant predictor of General Fatigue, Physical Fatigue and Reduced Activity. There were no significant predictors of Mental Fatigue.Multidimensional fatigue is common and severe in patients with pulmonary hypertension. Phosphodiesterase inhibitor plus endothelin receptor antagonist combination resulted in lower scores in most fatigue dimensions. Comprehensive assessment of fatigue should be considered in the clinical care of patients with pulmonary hypertension and clinical research to develop formal interventions that target this disabling symptom.

scholarly journals Gene Expression of Endothelin-1 and Endothelin Receptor A on Monocrotaline-Induced Pulmonary Hypertension in Rats After Bosentan Treatment

2010 ◽  
Vol 40 (9) ◽  
pp. 459 ◽  
Author(s):  
Kyoung Ah Lim ◽  
Kwan Chang Kim ◽  
Min-Sun Cho ◽  
Bo En Lee ◽  
Hae Soon Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pulmonary Hypertension ◽  
Endothelin Receptor ◽  
Endothelin 1 ◽  
Endothelin Receptor A
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