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.

Pulmonary vascular dysfunction in metabolic syndrome

“…; Moral‐Sanz et al . ); however, there is a slightly higher sensitivity to hypoxia in T1D rats than in control rats (Moral‐Sanz et al . ).…”

“…); however, there is a slightly higher sensitivity to hypoxia in T1D rats than in control rats (Moral‐Sanz et al . ). We demonstrated that RVSP was slightly, but significantly, increased in T2D mice (both inducible T2D and KK mice) compared to the controls.…”

Obesity and Pulmonary Hypertension: A Review of Pathophysiologic Mechanisms

“…Isolated pulmonary arteries of insulin resistant rats show diminished acetylcholine-mediated nitric oxide release, as well as upregulation of NADPH oxidase, 5-HT, and cycloxygenase-2 proteins [75–77]. Interestingly, in animal models, insulin resistance coupled with moderate hypoxia results in PH and right ventricular hypertrophy while neither insulin resistance nor hypoxemia alone induces PH or right ventricular hypertrophy [78]. Treatment with insulin sensitizing agents can reverse PH and attenuate pulmonary artery remodeling in insulin-resistant rodents [79, 80].…”

Chard (Beta vulgarisvar.cicla) extract improved hyperglycemia-induced oxidative stress and surfactant-associated protein alterations in rat lungs

“…Diabetes can potentially exacerbate inflammation, increase the production of proinflammatory cytokines, and enhance parenchymal infiltration of neutrophils and macrophages in rat lungs (Choi et al, 2008;Moral-Sanz et al, 2012). MPO, which is expressed abundantly in neutrophils, is a basic heme protein that utilizes chloride as a substrate and hydrogen peroxide as a co-substrate to generate ROS and free radical species that oxidatively modify lipids and proteins (Nauseef, 1986;Nauseef & Malech, 1986).…”