2026-04-14T19:47:26Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/700722025-01-13T07:43:22Zcom_10324_1149com_10324_931com_10324_894col_10324_1274

Olea Fraile, Elena Valverde Pérez, Esther Docio Cuadrado, Inmaculada Prieto Lloret, Jesús Aaronson, Philip Irving Rocher Martín, María Asunción 2024-09-20T11:16:56Z 2024-09-20T11:16:56Z 2024 International Journal of Molecular Sciences, 2024, Vol. 25, Nº. 13, 7484 1422-0067 https://uvadoc.uva.es/handle/10324/70072 10.3390/ijms25137484 7484 13 International Journal of Molecular Sciences 25 1422-0067 Producción Científica Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing increased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play important roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB dependence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima–media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of the exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter endothelial function or the contractile response to phenylephrine (PE) in these arteries. In contrast, CIH exposure increased the systemic arterial pressure and enhanced the contractile response to PE while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH. Ministerio de Economía, Comercio y Empresa (MINECO) y Fondo Europeo de Desarrollo Regional (FEDER) - (grant BFU2015-70616-R) Junta de Castilla y León, Consejería de Educación y Programa Estrategico IBGM - (grant CCVC8485) application/pdf eng MDPI info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/4.0/ © 2024 The authors Atribución 4.0 Internacional Pulmonary hypertension Hipertensión pulmonar Hipertensión arterial Hypoxia Anoxemia Respiratory organs -Diseases Organos respiratorios - Enfermedades Lungs - Blood-vessels - Diseases Pulmones - Vasos sanguíneos - Enfermedades Carotid body Cuerpo carotídeo Autonomic nervous system Nervioso Autónomo, Sistema Sleep apnea syndromes Síndrome de la apnea del sueño Endothelial function Endotelio vascular Guinea pig Animales de laboratorio Medicine 3205.08 Enfermedades Pulmonares 32 Ciencias Médicas Pulmonary vascular responses to chronic intermittent hypoxia in a guinea pig model of obstructive sleep apnea info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://www.mdpi.com/1422-0067/25/13/7484 SI