Maternal adaptations to pregnancy in spontaneously hypertensive rats: leptin and ghrelin evaluation

Abstract

Leptin and/or ghrelin, initially thought to be considered messengers of energy metabolism, are now considered to play a role in normal and complicated pregnancy. In this study, pregnant, spontaneously hypertensive rats (SHR) have been used to evaluate, for the first time, the modification of leptin and ghrelin both at serum and tissue levels. In SHR, we evaluate plasma leptin level and tissue protein expression in both placenta and adipose tissue at the end of gestation (day 20) versus normotensive Wistar-Kyoto (WKY) animals. The expression of functional leptin receptor (Ob-Rb) in peripheral tissues and in the hypothalamus was evaluated. Moreover, we measured plasma ghrelin level and its mRNA expression in the stomach and placenta. SHR strain presented significantly lower plasma leptin levels when compared with those found in pregnant or not WKY controls. Interestingly, in the placenta, leptin gene expression was higher in SHR than normotensive WKY. Moreover, we demonstrated a resistance to the effects of leptin via 'downregulation' of hypothalamic receptors in pregnant SHR. Conversely, SHR presented significantly higher ghrelin plasma levels when compared with those found in pregnant or not WKY. However, we observed that ghrelin level in the stomach of SHR did not change during pregnancy, and on the opposite, mRNA ghrelin in the placenta of SHR was lower than that of normotensive rats, suggesting a different production of this hormone in the fetal-placental unit. These data gain further insight into metabolic hormone modifications observed in a model of pre-existing hypertension associated with pregnancy.

Maternal Adaptation in Pregnant Hypertensive Rats: Improvement of Vascular and Inflammatory Variables and Oxidative Damage in the Kidney

“…Conversely, in agreement with previous findings in SHR, pregnancy remarkably reduced blood pressure 18 and HR near delivery. 2,6 Here, we investigated the mechanisms underling the normalization of pressure at the end of pregnancy: for the first time we evaluated the modification of ANG receptor subtypes (AT1 and AT2) expression in the kidney of these animals.…”

“…Systolic blood pressure (SBP) and heart rate (HR) were measured in conscious rats with a noninvasive common indirect method using a tail-cuff device in combination with blood flow sensor and recorder (Biological Research Apparatus; Ugo Basile, Comerio, Italy). 6 Briefly, rats were housed for 30 min in a warmed room (28-30 °C), then a tail cuff was placed ~2 cm from the base of the tail for measuring SBP. Care was taken in selecting an appropriate cuff size for each animal.…”

“…Moreover, other authors found a remarkable reduction of pressure at delivery. [3][4][5][6] However, the molecular mechanisms behind the modified hypertensive state during pregnancy remain to be elucidated. Among many vasomotor systems regulating blood pressure, the renin-angiotensin system (RAS) plays a pivotal role by regulating renal microvascular and tubular function.…”

Ghrelin and Cardiovascular Diseases

“…Pregnant, spontaneously hypertensive rats (SHR) exhibit significantly higher plasma ghrelin levels when compare with those of pregnant or normotensive Wistar-Kyoto (WKY) animals. In contradistinction, the mRNA of ghrelin in the placenta of SHR was lower than that of normotensive rats, suggesting a possible association of ghrelin and hypertension during pregnancy [65]. Makino and colleagues investigated the ghrelin concentrations in plasma of non-pregnant women, normal pregnant women, patients with pregnancy-induced hypertension, and postpartum women and they reported a negative correlation between plasma ghrelin concentration and systemic BP in normal pregnant women.…”

Ghrelin and Cardiovascular Diseases

“…Pregnant, spontaneously hypertensive rats (SHR) exhibit significantly higher plasma ghrelin levels when compare with those of pregnant or normotensive Wistar-Kyoto (WKY) animals. In contradistinction, the mRNA of ghrelin in the placenta of SHR was lower than that of normotensive rats, suggesting a possible association of ghrelin and hypertension during pregnancy [65]. Makino and colleagues investigated the ghrelin concentrations in plasma of nonpregnant women, normal pregnant women, patients with pregnancy-induced hypertension, and postpartum women and they reported a negative correlation between plasma ghrelin concentration and systemic BP in normal pregnant women.…”