Maternal high-sodium intake affects the offspring' vascular renin-angiotensin system promoting endothelial dysfunction in rats.

Perinatal sodium overload induces endothelial dysfunction in adult offspring, but the underlying mechanisms are not fully known. The involvement of tissue renin-angiotensin system on high sodium-programmed endothelial dysfunction was examined. Acetylcholine and angiotensin I and II responses were analyzed in aorta and mesenteric resistance arteries from 24-week-old male offspring of normal-salt (O-NS, 1.3% NaCl) and high-salt (O-HS, 8% NaCl) fed dams. COX-2 expression, O production and angiotensin converting enzyme (ACE) activity were determined. A separated O-HS was treated with losartan (15 mg kg/day) for eight weeks. Compared to O-NS, O-HS were normotensive. Acetylcholine-induced relaxation was impaired in O-HS arteries, which was improved by tempol, apocynin or indomethacin. The angiotensin I-induced contraction was greater in O-HS arteries, whereas the angiotensin II responses were unchanged. ACE activity, O production and COX-2 expression were increased in O-HS arteries. In this group, the increased O production was inhibited by apocynin or losartan. Chronic losartan decreased COX-2 expression and restored the endothelium-dependent vasodilation in O-HS. Our findings reiterate that perinatal sodium overload programs endothelial dysfunction in adult offspring through a blood pressure-independent mechanism. Our results also suggest that vascular angiotensin II is the main mediator of high sodium-programmed endothelial dysfunction, promoting COX-2 expression and oxidative stress.