Whole-body basal nitric oxide production is impaired in postprandial endothelial dysfunction in healthy rats.
In healthy humans, a high-saturated-fat/high-sucrose meal induces vascular endothelial dysfunction, a hallmark of atherogenesis. This transient dysfunction indicates a loss in nitric oxide (NO) production and/or bioactivity in the vasculature but it remains unknown if this is the local manifestation of a general impairment in NO pathway in the postprandial state. Here, we studied whole-body NO production and systemic NO bioactivity in postprandial endothelial dysfunction, as induced by a high-saturated-fat, high-sucrose meal. We first developed a physiological test of endothelial function on conscious rats, based on the transient fall in blood pressure after iv acetylcholine, and showed that this response was NO-dependent. As assessed with this method in healthy rats, endothelial function decreased during the postprandial state, being 60+/-7% lower than baseline at 6h after the meal challenge, associated with important elevations in plasma triglycerides and hydroperoxides. Aortic superoxide anion production, as assessed by oxidative fluorescent detection, was higher 6h after the meal challenge than after the nutrients vehicle (water). During the postprandial period, plasma cGMP, but not plasma ANP, markedly decreased, indicating a general decrease in NO bioavailability, which was numerically maximal 4h after the meal challenge. As determined 4h after ingestion by a tracer-based method using iv [(15)N(2)-(guanido)]-arginine, the whole-body NO production fell by 27+/-9% postprandially. This is the first study evidencing that a meal challenge that impairs the stimulated, NO-mediated, vascular response also reduces whole-body basal NO production and bioavailability. Postprandial pathophysiology may build on this general, fundamental alteration in NO production.
AgroParisTech, CRNH-IdF, UMR914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France.
Joëlle
J
Magné
Jean François
JF
Huneau
Stéphanie
S
Delemasure
Luc
L
Rochette
Daniel
D
Tomé
François
F
Mariotti
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001682:Biological Availability; D015415:Biomarkers / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D003627:Data Interpretation, Statistical; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D018384:Oxidative Stress; D019518:Postprandial Period / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D014280:Triglycerides; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D000109:Acetylcholine