Maladaptive Pulmonary vascular responses to chronic intermittent and sustained hypoxia in a rat hypertension model

Resumen del trabajo presentado al European Respiratory Society (ERS) International Congress, celebrado en Paris (Francia) del 15 al 19 de septiembre de 2018.
[Rationale & Aim]: Chronic sustained hypoxia (CSH) initiates physiological adaptations to maintain oxygen levels but also has deleterious effects as pulmonary hypertension (PH). Chronic intermittent hypoxia (CIH), as found in obstructive sleep apnea, is associated with the development of systemic hypertension and cardiovascular pathologies. Our aim was to compare systemic and pulmonary hypertension and endothelial dysfunction development in rats exposed to CSH vs. CIH.
[Methods]: We exposed male rats to sustained hypoxic atmosphere (10%O2; pO2≈70 mmHg, 14 days) or intermittent hypoxia (5%O2 40s, 21%O2 80s, 8h/day, 21 days). We measured pulmonary artery (PA) pressure by right heart catheterization, Fulton index, vasomotor responses in PA using small vessels myography and L- arginine-NO metabolism.
[Results]: Systemic and pulmonary hypertension, besides left ventricular hypertrophy, occurs in response to CIH exposure in rats, preserving pulmonary artery endothelial integrity, but decreasing NO production and eNOS protein expression. Conversely, CSH exposure triggers CB mediated respiratory chemoreflex, PH and right ventricular hypertrophy, besides blunted pulmonary vascular relaxation to carbachol and reduced plasma L-arginine: asymmetric dimethyl arginine (ADMA) ratio.
[Conclusion]: CSH and CIH point to different targets and different mechanisms to produce endothelial dysfunction and systemic and pulmonary hypertension in the rat.
Spanish Ministry of Economy and Competitiveness, MINECO/FEDER, UE (BFU2015-70616-R); CIBER Enfermedades Respiratorias, ISCiii (CIBERES, CB06/06/0050).