Key result
Sustained-release sodium nitrite enhanced myocardial NO bioavailability, attenuated oxidative stress, and improved ex vivo coronary artery vasorelaxation in a porcine model of metabolic syndrome.
Why the study?
Metabolic syndrome reduces endothelial nitric oxide bioavailability and exacerbates vascular dysfunction, and the effects of sustained-release nitrite therapy on myocardial protection in this context were not characterized.
May support nitrite therapy in MetS vascular dysfunction; leaves open translation from swine models to clinical use.
Metabolic syndrome (MetS) reduces endothelial nitric oxide (NO) bioavailability and exacerbates vascular dysfunction in patients with preexisting vascular diseases. Nitrite, a storage form of NO, can mediate vascular function during pathological conditions when endogenous NO is reduced. The aims of the present study were to characterize the effects of severe MetS and obesity on dyslipidemia, myocardial oxidative stress, and endothelial NO synthase (eNOS) regulation in the obese Ossabaw swine (OS) model and to examine the effects of a novel, sustained-release formulation of sodium nitrite (SR-nitrite) on coronary vascular reactivity and myocardial redox status in obese OS subjected to critical limb ischemia (CLI). After 6 mo of an atherogenic diet, obese OS displayed a MetS phenotype. Obese OS had decreased eNOS functionality and NO bioavailability. In addition, obese OS exhibited increased oxidative stress and a significant reduction in antioxidant enzymes. The efficacy of SR-nitrite therapy was examined in obese OS subjected to CLI. After 3 wk of treatment, SR-nitrite (80 mg · kg(-1) · day(-1) bid po) increased myocardial nitrite levels and eNOS function. Treatment with SR-nitrite reduced myocardial oxidative stress while increasing myocardial antioxidant capacity. Ex vivo assessment of vascular reactivity of left anterior descending coronary artery segments demonstrated marked improvement in vasoreactivity to sodium nitroprusside but not to substance P and bradykinin in SR-nitrite-treated animals compared with placebo-treated animals. In conclusion, in a clinically relevant, large-animal model of MetS and CLI, treatment with SR-nitrite enhanced myocardial NO bioavailability, attenuated oxidative stress, and improved ex vivo coronary artery vasorelaxation.
No takes yet. Share an insight, caveat, or question.
Bradley et al. (2015) studied Metabolic syndrome and critical limb ischemia. Sustained-release sodium nitrite (SR-nitrite) vs. Placebo was evaluated on Myocardial NO bioavailability, oxidative stress, and ex vivo coronary artery vasorelaxation. Sustained-release sodium nitrite enhanced myocardial NO bioavailability, attenuated oxidative stress, and improved ex vivo coronary artery vasorelaxation in a porcine model of metabolic syndrome.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: