Influence of Obesity on Vascular Dysfunction Following Traumatic Hemorrhage.

BACKGROUND: Obesity increases the risk for morbidity and mortality following trauma. These complications are associated with profound vascular damage. Traumatic hemorrhage acutely attenuates vascular responsiveness, but the impact of obesity on this dysfunction is not known. The local inflammatory response in vascular cells is also unknown. We hypothesized that obesity potentiates trauma-induced vascular inflammation and dysfunction.

METHODS: Male Sprague-Dawley rats (~250 g) were fed normal chow (NC; 13.5% kcal fat, n = 20) or high-fat (HF; 60% kcal fat, n = 20) diets for 6-8 weeks. Under anesthesia, hemorrhage was induced by a mesenteric artery laceration, a Grade V splenic injury, and hypotension (MAP = 30-40 mmHg) for 30 minutes. Vascular responsiveness was assessed ex vivo in isolated mesenteric arteries pre- and post-hemorrhage. Gene expression for interleukin (IL)-1β, and IL-6, pro-oxidant NADPH oxidase 2 (NOX2), and α-adrenergic receptor were assessed in carotid artery endothelial cells (ECs) and non-ECs (media + adventitia).

RESULTS: In NC rats, hemorrhage attenuated norepinephrine-induced vasoconstriction and endothelium-dependent vasodilation to acetylcholine. In HF rats, baseline norepinephrine-induced vasoconstriction was attenuated compared to NC, but vasoconstriction and endothelium-dependent vasodilation did not change pre- to post-hemorrhage. Hemorrhage led to elevated IL-1β gene expression in ECs, and elevated IL1β, IL-6, NOX2, and α-adrenergic receptor gene expression in the media + adventitia compared with sham. HF rats had greater EC IL-1 β and NOX2 gene expression compared with NC rats. The hemorrhage-induced elevation of IL-1β in the media + adventitia was greatest in HF rats.

CONCLUSION: Traumatic hemorrhage attenuates vascular responsiveness and induces vascular inflammation. The attenuated vascular responsiveness following hemorrhage is absent in obese rats, while the elevated vascular inflammation persists. A HF diet amplifies the arterial inflammation after hemorrhage. Altered vascular responsiveness and vascular inflammation may contribute to worse outcomes in obese trauma patients.