Maternal melatonin or agomelatine therapy prevents programmed hypertension in male offspring of mother exposed to continuous light†

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Abstract
Hypertension can originate from early-life insults, whereas maternal melatonin therapy can be protective in a variety of models of programmed hypertension. We hypothesize that melatonin or melatonin receptor agonist agomelatine can prevent programmed hypertension in adult offspring induced by maternal exposure to continuous light. Female Sprague-Dawley pregnant rats randomly divided into four groups: controls, rats exposed to continuous light, exposed to continuous light plus treated with agomelatine (50 mg/day i.p.), and exposed to continuous light plus treated with 0.01% melatonin in drinking water throughout pregnancy and lactation period. Male offspring (n = 10/group) from three litters were examined at 12 weeks of age. Maternal continuous light exposure-induced hypertension in male offspring, which was prevented by melatonin or agomelatine therapy. Continuous light exposure did not affect melatonin pathway in adult offspring kidney. Genes that belong to the renin-angiotensin system (RAS), sodium transporters, AMP-activated protein kinase pathway, and circadian rhythm were potentially involved in the maternal exposure to continuous light-induced programmed hypertension. Maternal agomelatine therapy decreased Ace expression but increased Agtr2 and Mas1. Maternal melatonin therapy prevented the increases of Slc9a3, Slc12a3, and Atp1a1 expression induced by maternal continuous light exposure. In conclusion, maternal melatonin or agomelatine therapy prevents programmed hypertension induced by maternal exposure to continuous light. Agomelatine and melatonin reprogram the RAS and sodium transporters differentially, to prevent negative programming of continuous light. Our data highlight candidate genes and pathways in renal programming as targets for therapeutic approaches to prevent programmed hypertension caused by early-life disturbance of the circadian rhythm.

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