Pregnancy-Induced Hypertension is Associated with an Activation of Endothelial Cells

Abstract

Objective: The study examined the effects of salt-induced hypertension on vascular contractile responses during pregnancy and the mechanisms of the effects.

Methods: Aortic rings from pregnant Wistar rats, fed for 6 weeks on diets containing 0.3% (control) and 8.0% (test) sodium chloride were contracted by phenylephrine, 5-hydroxytryptamine, and potassium chloride, in the presence and absence of either endothelium or 10⁻⁶ M indomethacin. Contractile responses to calcium chloride were also assessed.

Results: High salt intake increased the systolic blood pressure of the rats. Rings from the high-salt-fed rats showed enhanced reactivity to phenylephrine, but not to potassium chloride and 5-hydroxytryptamine. Indomethacin treatment decreased the contractions of rings from the test rats to phenylephrine, but did not significantly affect the responses of rings from the control rats. Removal of endothelium resulted in similar increase in the contractile responses of rings from both groups of rats to phenylephrine but had no effect on responses to 5-hydroxytryptamine and potassium chloride. Rings from hypertensive rats showed significantly increased maximal contractions to calcium chloride when pretreated with phenylephrine but not potassium chloride. Contractile responses to phenylephrine in calcium-free medium were similar in both groups of rats.

Conclusions: The results suggest that the enhanced contractions of aortic rings from pregnant rats with salt-induced hypertension are related to alterations in adrenergic mechanisms, and are mediated by vasoconstrictor prostaglandin and enhanced calcium influx through a phenylephrine-activated receptor operated calcium entry pathway. The capacity to produce endothelium-dependent relaxation appears unaltered in this form of hypertension in pregnancy.

Objective: The aim of the study was to elucidate the biochemical and structural basis of the modifications in endothelial functions recently described in pregnancy-induced hypertension (PIH).

Methods: Umbilical cords were obtained from 6 healthy pregnant women and 6 women affected by PIH. Endothelial cells were prepared by an adaptation of the method of Jaffe et al. The fluidity of the cellular membrane was assayed by the fluorescent probe l-(4-trimethylaminophenyl)-6-phenyl-l,3,5-hexatriene (TMA-DPH). The fluid-phase endocytosis of the cells was studied by the measurement of the probe fraction internalized by endocytosis as described by Illinger. The morphological study was performed by transmission electron microscopy (TEM).

Results: In comparison with endothelial cells from controls the cells from PIH women showed: (i) a significant decrease in the anisotropy values of TMA-DPH (P<0.01). indicating an increased membrane fluidity; (ii) a higher relative fluorescence intensity of TMA-DPH after 5-min incubation (P<0.01), consistent with an enhanced fluid-phase endocytosis; (iii) morphological features of activation with a hypertrophic Golgi apparatus and a dilated rough endoplasmic reticulum.

Conclusions: The present results indicate an activation of endothelial cells during PIH, which might per se affect the vascular reactivity through modifications in the endothelial synthesis of vasoactive molecules.

Key Words:

• Mechanisms
• Pregnancy
• Salt-induced hypertension
• Electron microscopy study
• Endocytosis
• Endothelial cell
• Membrane fluidity
• Pregnancy-induced hypertension