title: Different patterns of pulmonary vascular disease induced by type 1 diabetes and moderate hypoxia in rats.
abstract: Although type 1 and type 2 diabetes are strongly associated with systemic cardiovascular morbidity, the relationship with pulmonary vascular disease had been almost disregarded until recent epidemiological data revealed that diabetes might be a risk factor for pulmonary hypertension. Recent experimental studies suggest that diabetes induces changes in lung function insufficient to elevate pulmonary pressure. The aim of this study was to assess the effects of diabetes on the sensitivity to other risk factors for pulmonary hypertension. We therefore analysed the effects of the combination of diabetes with exposure to moderate hypoxia on classical markers of pulmonary hypertension. Control (saline-treated) and diabetic (70 mg kg(-1) streptozotocin-treated) male Wistar-Kyoto rats were followed for 4 weeks and exposed to normoxia or moderate normobaric hypoxia (14%) for another 2 weeks. Hypoxia, but not diabetes, strongly reduced voltage-gated potassium currents, whereas diabetes, but not hypoxia, induced pulmonary artery endothelial dysfunction. Both factors independently induced pulmonary vascular remodelling and downregulated the lung bone morphogenetic protein receptor type 2. However, diabetes, but not hypoxia, induced pulmonary infiltration of macrophages, which was markedly increased when both factors were combined. Diabetes plus hypoxia induced a modest increase in diastolic and mean pulmonary artery pressure and right ventricular weight, while each of the two factors alone had no significant effect. The pattern of changes in markers of pulmonary hypertension was different for moderate hypoxia and diabetes, with no synergic effect except for macrophage recruitment, and the combination of both factors was required to induce a moderate elevation in pulmonary arterial pressure.
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico, San Carlos (IdISSC), Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Moral-Sanz
authors.forename: Jose G
authors.initials: JG
authors.lastname: Lopez-Lopez
authors.forename: Carmen
authors.initials: C
authors.lastname: Menendez
authors.forename: Enrique
authors.initials: E
authors.lastname: Moreno
authors.forename: Bianca
authors.initials: B
authors.lastname: Barreira
authors.forename: Daniel
authors.initials: D
authors.lastname: Morales-Cano
authors.forename: Lucia
authors.initials: L
authors.lastname: Escolano
authors.forename: Pilar
authors.initials: P
authors.lastname: Fernandez-Segoviano
authors.forename: Eduardo
authors.initials: E
authors.lastname: Villamor
authors.forename: Angel
authors.initials: A
authors.lastname: Cogolludo
authors.forename: Francisco
authors.initials: F
authors.lastname: Perez-Vizcaino
authors.forename: Laura
authors.initials: L
authors.lastname: Moreno
mesh_terms: D000818:Animals; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D015536:Down-Regulation; D006976:Hypertension, Pulmonary / Q000209:etiology*; D017380:Hypertrophy, Right Ventricular / Q000209:etiology; D000860:Hypoxia / Q000150:complications*; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011921:Rats, Inbred WKY; D014652:Vascular Diseases / Q000209:etiology
chemical_list: D052006:Bone Morphogenetic Protein Receptors, Type II