Related Experiment Video
Updated: Apr 29, 2026
Human Primary Trophoblast Cell Culture Model to Study the Protective Effects of Melatonin Against Hypoxia/reoxygenation-induced Disruption
Published on: July 30, 2016
Melatonin therapy prevents programmed hypertension and nitric oxide deficiency in offspring exposed to maternal
You-Lin Tain1, Li-Tung Huang2, Chien-Ning Hsu3
1Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan ; Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan.
Insights
Maternal calorie restriction programs hypertension in offspring by reducing nitric oxide (NO). Melatonin therapy prevents this programmed hypertension by restoring NO levels and influencing epigenetic gene expression.
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Nutritional Science
Background:
- Nitric oxide (NO) deficiency is linked to hypertension development, which can manifest early in life.
- Programmed hypertension in offspring may arise from maternal dietary factors during gestation.
Purpose of the Study:
- To investigate if maternal calorie restriction (CR) programs hypertension in rat offspring due to NO deficiency.
- To determine if maternal melatonin therapy can prevent CR-induced programmed hypertension in offspring.
Main Methods:
- Examined 3-month-old male rat offspring from control, CR, control + melatonin, and CR + melatonin maternal groups.
- Analyzed plasma asymmetric dimethylarginine (ADMA), L-arginine, L-arginine-to-ADMA ratio (AAR), and renal NO production.
- Assessed effects on nephrogenesis, renin-angiotensin system components, and global gene expression via next-generation sequencing.
Main Results:
- CR offspring exhibited hypertension, elevated ADMA, decreased L-arginine, reduced AAR, and diminished renal NO production.
- Maternal melatonin treatment normalized these parameters, preventing hypertension development in CR offspring.
- Melatonin therapy also modulated renin-angiotensin system components and induced long-term epigenetic changes in kidney gene expression.
Conclusions:
- Maternal calorie restriction programs hypertension in offspring, associated with NO deficiency and altered renin-angiotensin system activity.
- Maternal melatonin therapy effectively prevents programmed hypertension by restoring NO bioavailability, normalizing the L-arginine/ADMA ratio, and mediating epigenetic modifications.
Abstract:
Nitric oxide (NO) deficiency is involved in the development of hypertension, a condition that can originate early in life. We examined whether NO deficiency contributed to programmed hypertension in offspring from mothers with calorie-restricted diets and whether melatonin therapy prevented this process. We examined 3-month-old male rat offspring from four maternal groups: untreated controls, 50% calorie-restricted (CR) rats, controls treated with melatonin (0.01% in drinking water), and CR rats treated with melatonin (CR + M). The effect of melatonin on nephrogenesis was analyzed using next-generation sequencing. The CR group developed hypertension associated with elevated plasma asymmetric dimethylarginine (ADMA, a nitric oxide synthase inhibitor), decreased L-arginine, decreased L-arginine-to-ADMA ratio (AAR), and decreased renal NO production. Maternal melatonin treatment prevented these effects. Melatonin prevented CR-induced renin and prorenin receptor expression. Renal angiotensin-converting enzyme 2 protein levels in the M and CR + M groups were also significantly increased by melatonin therapy. Maternal melatonin therapy had long-term epigenetic effects on global gene expression in the kidneys of offspring. Conclusively, we attributed these protective effects of melatonin on CR-induced programmed hypertension to the reduction of plasma ADMA, restoration of plasma AAR, increase of renal NO level, alteration of renin-angiotensin system, and epigenetic changes in numerous genes.
More Related Videos
Related Concept Videos
01:29Hypertension II: Pathophysiology
01:17Hormonal Regulation of Blood Pressure
Epinephrine and Norepinephrine
The adrenal medulla releases epinephrine and norepinephrine, catecholamines that enhance and extend the sympathetic or "fight or flight" physiological response. These hormones escalate heart rate and the force of contraction...
01:18Hypertension and Regulation of Blood Pressure
01:19Management of Insomnia
01:18Neural Regulation of Blood Pressure
Baroreceptor Reflex
Baroreceptors, located in the carotid sinuses and aortic arch, detect changes in blood pressure. When blood pressure rises, these stretch-sensitive receptors...
01:15Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...