Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm

Abstract

Non-dipping circadian blood pressure (BP) is a common finding in preeclampsia, accompanied by adverse outcomes. Melatonin plays pivotal role in biological circadian rhythms. This study investigated the relationship between melatonin secretion and circadian BP rhythm in preeclampsia. Cases were women with preeclampsia treated between January 2006 and June 2007 in the University Hospital of Larissa. Volunteers with normal pregnancy, matched for chronological and gestational age, served as controls. Twenty-four hour ambulatory BP monitoring was applied. Serum melatonin and urine 6-sulfatoxymelatonin levels were determined in day and night time samples by enzyme-linked immunoassays. Measurements were repeated 2 months after delivery. Thirty-one women with preeclampsia and 20 controls were included. Twenty-one of the 31 women with preeclampsia were non-dippers. Compared to normal pregnancy, in preeclampsia there were significantly lower night time melatonin (48.4 ± 24.7 vs. 85.4 ± 26.9 pg/mL, p50.001) levels. Adjustment for circadian BP rhythm status ascribed this finding exclusively to non-dippers (p50.01). Two months after delivery, in 11 of the 21 non-dippers both circadian BP and melatonin secretion rhythm reappeared. In contrast, in cases with retained non-dipping status (n ¼ 10) melatonin secretion rhythm remained impaired: daytime versus night time melatonin (33.5 ± 13.0 vs. 28.0 ± 13.8 pg/mL, p ¼ 0.386). Urinary 6-sulfatoxymelatonin levels were, overall, similar to serum melatonin. Circadian BP and melatonin secretion rhythm follow parallel course in preeclampsia, both during pregnancy and, at least 2 months after delivery. Our findings may be not sufficient to implicate a putative therapeutic effect of melatonin, however, they clearly emphasize that its involvement in the pathogenesis of a non-dipping BP in preeclampsia needs intensive further investigation.

Measuring of Plasma Melatonin Level in Patients with Preeclampsia

“…The result in the current study showed that all (20)healthy pregnant women have the physiological rhythm of BP and normal levels of plasma melatonin secretion at daytime and nighttime measurement , while 20 women with preeclampsia were of two groups , the dipping group were have the normal physiological rhythm of BP and melatonin secretion of daytime and nighttime melatonin secretion , the second or nondipping group the BP did not show the normal nocturnal dipping and nocturnal melatonin secretion was decreased of daytime and nighttime compared to normal healthy pregnant women and dipping group with PE . This is concordant with that revealed by Bouchlariotou et al2014 (23) whom study included 51 women that measuring serum and urine melatonin levels ,20 women of normal healthy pregnancy all were dipper with normal melatonin secretion and 31 women with preeclampsia, women with preeclampsia (68%) non-dipper with reduced nighttime melatonin secretion (P value< 0.001) compared to normal healthy pregnant women , and (32%) were dippers with normal rhythm of BP and daytime , nighttime melatonin secretion. Also concordant with that revealed by Nakamura et al 2001 (23),study showed serum melatonin secretion in preeclampsia significantly lower than serum melatonin secretion of normal pregnant women after 32 weeks of gestation .…”

“…This is concordant with that revealed by Bouchlariotou et al2014 (23) whom study included 51 women that measuring serum and urine melatonin levels ,20 women of normal healthy pregnancy all were dipper with normal melatonin secretion and 31 women with preeclampsia, women with preeclampsia (68%) non-dipper with reduced nighttime melatonin secretion (P value< 0.001) compared to normal healthy pregnant women , and (32%) were dippers with normal rhythm of BP and daytime , nighttime melatonin secretion. Also concordant with that revealed by Nakamura et al 2001 (23),study showed serum melatonin secretion in preeclampsia significantly lower than serum melatonin secretion of normal pregnant women after 32 weeks of gestation . Also concordant with that revealed by Zeng et al2016 (26), serum was collected from women with preeclampsia the serum levels of melatonin were significantly reduced in women with preeclampsia at presentation , while its inconsistent with Tranquilly et al 2004 (27),study of 16 primigravidae showed the rhythm of melatonin secretion was lost in all pregnant women with lost of blood pressure rhythm and preeclamptic women have higher melatonin concentrations (P value<0.001) , this may be due to small sample size and in present study we carefully selected patient ages (20-30) because melatonin secretion is age-related secretion that higher levels in children and the lower levels in elderlies and to avoid age-related differences we selected age ranges between (20 -30) years old .…”

“…2014 (23) who also found no relationship between severe and non-severe cases of preeclampsia and melatonin levels (p value 0.106) . This is concordant with Zeng et al (2016) (26) ,who showed that reduced levels of melatonin in patients with preeclampsia not associated with the severity of preeclampsia .…”

“…Blood pressure (BP) in healthy individuals follows a characteristic circadian pattern with a nocturnal decline of 10-20% followed by an increase early in the morning. (23) In some patients with hypertension or chronic kidney disease however, BP fails to dip during night and these individuals have been called ''non-dippers'', in contrast with those with a normal nocturnal dip, who are called ''dippers''. Melatonin influences rhythmic changes in BP by affecting the master clock localized in the suprachiasmatic nucleus of the hypothalamus, so present study aimed to correlate Melatonin level and its use as marker for severity of preeclampsia.…”

The Role of Prenatal Melatonin in the Regulation of Childhood Obesity

“…There is a decrease in placental α7nAChR mRNA and protein in women with preeclampsia [110], indicating that this would be correlated with the decrease in placental melatonin production that is also evident in this condition [111]. Preeclampsia is also associated with a decrease in pineal melatonin, which may be especially evident in preeclamptic women with non-dipping nighttime blood pressure [112]. Melatonin's positive regulation of the α7nAChR may also directly regulate obesity, since α7nAChR agonism is associated with decreased food intake [113].…”