Impaired pulmonary vasomotor control in exercising swine with multiple comorbidities.

Autor: van de Wouw J; Division of Experimental Cardiology, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands., Steenhorst JJ; Division of Experimental Cardiology, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands., Sorop O; Division of Experimental Cardiology, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands., van Drie RWA; Division of Experimental Cardiology, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands., Wielopolski PA; Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Kleinjan A; Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Hirsch A; Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.; Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Duncker DJ; Division of Experimental Cardiology, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands., Merkus D; Division of Experimental Cardiology, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. d.merkus@erasmusmc.nl.; Institute for Surgical Research, Walter Brendel Center of Experimental Medicine (WBex), University Clinic Munich, LMU Munich, Munich, Germany. d.merkus@erasmusmc.nl.; German Center for Cardiovascular Research, Partner Site Munich, Munich Heart Alliance, Munich, Germany. d.merkus@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Basic research in cardiology [Basic Res Cardiol] 2021 Sep 12; Vol. 116 (1), pp. 51. Date of Electronic Publication: 2021 Sep 12.
DOI: 10.1007/s00395-021-00891-7
Abstrakt: Pulmonary 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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