부산대학교 도서관

A poor developmental environment increases the risk of cardiovascular disease in humans; this is modelled by protein restriction (PR) during pregnancy in rats. Chronic statin treatment in the PR model from an early age restores endothelial function while an acute early age angiotensin blockade reduces blood pressure long term. The aim of this study was to investigate if acute early age statin treatment could improve vascular function long term in the PR offspring. Female Wistar rats were fed control (18 % protein) or PR (9% casein) diet throughout pregnancy. Subgroups of the offspring from both maternal groups received atorvastatin (10 mg/kg/day) in their drinking water from three to five weeks of age. Vascular reactivity was assessed at five and sixteen weeks. Components of the vasoreactivity signalling pathways were investigated with real-time PCR and Western blotting. Maternal PR did not alter vascular function in the offspring and the effects of statin treatment were independent of maternal diet. At five weeks of age maximal constriction to phenylephrine was reduced in the statin treated male offspring aortae (p<0.01). Conversely, at sixteen weeks maximal constriction was increased of male (p<0.05) and female (p<0.01) statin treated offspring mesenteric arteries. RhoA and ROCK1 mRNA levels were increased in statin treated offspring mesenteric arteries at sixteen weeks (p<0.05). Statin treatment had no effect on NO-mediated vasorelaxation. This study shows that early age acute statin treatment has both short and long term effects on cardiovascular function and molecular markers in rats. The long term effects appear to have arisen as a consequence of the withdrawal rather than being a direct effect of the statin treatment adding to the emerging evidence of a rebound effect after statin withdrawal. The RhoA pathway is indicated as the mechanisms behind the effects of statin withdrawal in this study.