Nitric oxide stores in coronary blood vessels of dogs with metabolic syndrome

Abstract

Nitric oxide (NO) in vivo forms complexes (NO stores) for transport and intracellular storage of NO. A key function of NO stores is defense against NO toxicity during NO overproduction. Metabolic syndrome (MS) is associated with NO overproduction, which is detrimental for endothelium function. We evaluated NO storage in coronary vessels of 4 dogs with MS induced by a high fat diet and in coronary vessels of 4 control dogs. NO stores were indexed by relaxation of isolated left circumflex artery (LCA) rings, precontracted with a thromboxane A2 mimetic, U46619 (625 nmol/L), to N‐acetylcysteine (NAC, 10−3 M). NAC‐induced relaxation of LCA from dogs with MS was larger than in control (11.1±1.6 vs 3.1±1.4%, respectively, P<0.01). This is consistent with NO overproduction in MS. To estimate capacity of NO stores, LCA was incubated with a NO donor, dinitrosyl iron complex (10−5 M) for 20 min. After washout, LCA was precontracted with U46619, and NAC was added to release NO from the accumulated NO stores. Relaxation of LCA from control dogs was significantly greater than that of LCA from dogs with MS (62.4±7.3 vs. 33.9±5.9%, respectively, P<0.03). In conclusion, our findings are consistent with NO overproduction in MS, and with depressed ability of MS coronary vessels to bind excessive NO into NO stores. Thus, an intrinsic defense of coronary vessels against NO toxicity is impaired in MS. (supported by CRI/Integrative Physiology, UNTHSC)