Pulmonary allergic reactions impair systemic vascular relaxation in ragweed sensitive mice

Abstract

Asthma is often associated with cardiovascular complications, and recent observations in animal models indicate that induction of pulmonary allergic inflammation increases susceptibility of the myocardium to ischemia and reperfusion injury. In this study, we used a murine model of allergen sensitization in which aspiration of allergen induces pulmonary and systemic inflammation, to test the hypothesis that pulmonary exposure to allergen alters vascular relaxation responses. BALB/C mice were sensitized by intra-peritoneal injection of ragweed and challenged by intratracheal instillation of allergen. Airway hyperreactivity and pulmonary inflammation were confirmed, and endothelium-dependent and -independent reactivity of thoracic aorta rings were evaluated. Ragweed-sensitization and challenge induced airway hyperreactivity to methacholine and pulmonary inflammation, but did not affect constrictor responses of the aortic rings to phenylephrine and K depolarization. In contrast, maximal relaxation of aortic rings to acetylcholine and sodium nitroprusside decreased from 87.6 ± 3.9 % and 97.7 ± 1.2 % to 32 ± 4 % and 51 ± 6 %, respectively (p< 0.05). The sensitivity to acetylcholine was likewise reduced (EC 50 = 0.26 ± 0.05 µM vs. 1.09 ± 0.16 µM, p < 0.001). The results demonstrate that induction of allergic pulmonary inflammation in mice depresses endothelium-dependent and -independent vascular relaxation, which can contribute to cardiovascular complications associated with allergic inflammation.

Severe asthma is associated with a remodeling of the pulmonary arteries in horses

“…This difference was not observed in vivo, with both groups showing similar low degree of collapse. Pulmonary arteries of asthmatic horses may show hypercontractility and impaired post-mortem relaxation similarly to what was previously demonstrated in experimental animal models of lung allergic inflammation [37][38][39]. However, differences in wall area (expression of wall thickening) were not affected by reactivity differences between groups and were similarly detected both in vivo and post-mortem, suggesting consistent remodeling of pulmonary artery walls in asthmatic horses.…”

Impact of pulmonary exposure to gold core silver nanoparticles of different size and capping agents on cardiovascular injury

“…We also recognize the potential importance of lipid oxidation that may occur and the close to ties to the oxidant/antioxidant balance that was not examined in this study but likely underlie the reports of oxidative stress following exposure. Our findings may support an alternative hypothesis for the general effect of a pulmonary exposure to EM, one in which the EM may not directly induce an significant initial inflammatory response but exacerbate an inflammatory response to a secondary insult, such as been described following inoculation with lipopolysaccharide (LPS) [ 52 ] or immune sensitization in asthma models associated with both vascular dysfunction and expansion of myocardial infarction [ 53 ]. Previous studies investigating the EMN exposure and pulmonary fibrosis in rats demonstrated that exposure to nanomaterials alone were insufficient to induce fibrosis.…”

Impact of airway challenges on cardiovascular risk in asthma – a randomized controlled trial

“…Most previous studies investigating cardiovascular risk in asthma have been observational. In this study, we attempted to provide the physiological link between asthma and elevated cardiovascular risk [ 2 – 4 ], and to confirm experimental work demonstrating that pulmonary inflammation leads to systemic inflammation conducted in animal models [ 14 , 15 ] in a clinical laboratory setting. Previous work observed small but statistically significant changes in systemic levels of CRP and IL-6 when exposing otherwise healthy people to a pro-inflammatory insult, which resulted in both elevated arterial stiffness [ 17 ] and impairments in endothelial function [ 16 ].…”

“…Findings from animal studies suggest that increased levels of systemic inflammation during asthma-like events originate in the lungs [ 14 , 15 ]. Indeed, markers of acute inflammation, such as C-reactive protein (CRP), are elevated in exhaled breath condensate during naturally occurring asthma exacerbations, and are correlated with CRP levels measured systematically at the same time-points [ 8 , 10 ].…”