title: Postnatal dexamethasone-induced programmed hypertension is related to the regulation of melatonin and its receptors.
abstract: Adulthood hypertension can be programmed by glucocorticoid exposure in early life. We found that maternal melatonin therapy prevents postnatal dexamethasone (DEX)-induced programmed hypertension. Melatonin acts through specific receptors, including MT1 and MT2 membrane receptors, and retinoid related orphan nuclear receptors of the RZR/ROR family. Thus we tested whether postnatal DEX-induced hypertension is related to changes of melatonin receptors in the kidney and heart, which was preserved by maternal melatonin therapy. Male neonates were assigned to four groups (n=6-8/group): control, DEX, control+melatonin (MEL), and DEX+MEL. Male rat pups were injected i.p. with DEX on d 1 (0.5 mg/kg BW), d 2 (0.3 mg/kg BW), and d 3 (0.1 mg/kg BW) after birth. Melatonin was administered in drinking water (0.01%) during the lactation period. We found DEX group developed hypertension at 16 weeks of age, which melatonin therapy prevented. Postnatal DEX treatment increased mRNA expression of MT1 and MT2, while decreased RORα and RZRβ in the kidney. These changes were prevented by melatonin therapy. Postnatal DEX decreased protein level of MT2 in the kidney, which was attenuated by melatonin therapy. Renal protein level of RORα was higher in DEX+MEL group compared to control and DEX group. Renal melatonin level was higher in the MEL and DEX+MEL groups compared to control. We concluded that melatonin therapy has long-term protection on postnatal DEX-induced programmed hypertension, which is associated with regulation on melatonin receptors in the kidney. Our findings would offer potential therapeutic approaches to prevent programmed hypertension in premature baby receiving glucocorticoids.
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hsin-Yu
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan. Electronic address: tainyl@hotmail.com.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Tain
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003907:Dexamethasone / Q000009:adverse effects*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000378:metabolism* / Q000494:pharmacology; D009035:Mothers; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044094:Receptors, Melatonin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D044094:Receptors, Melatonin; D003907:Dexamethasone; D008550:Melatonin
keywords: Developmental programming; Glucocorticoid; Hypertension; Melatonin; Melatonin receptor; Nuclear receptor