Endothelin, sex, and pregnancy: unique considerations for blood pressure control in females

Am J Physiol Regul Integr Comp Physiol. 2016 Apr 15;310(8):R691-6. doi: 10.1152/ajpregu.00427.2015. Epub 2016 Mar 2.

Abstract

Endothelin-1 (ET-1) is a potent vasoconstrictor, and dysregulation of the endothelin (ET) system has been implicated in the development of hypertension. Sex differences in the ET system have been identified in ET receptor expression and activation, levels of ET-1, and downstream mediators of the ET system. More specifically, males have greater ET-1/ETA receptor activation, whereas females exhibit greater ETB receptor activation. These differences have been suggested to contribute to the sex differences observed in blood pressure control, with greater ETB receptor activation in females potentially acting as an important pathway contributing to the lower prevalence of hypertension in young females compared with age-matched males. This hypothesis is further supported by studies in pregnancy; the role of the ET system is enhanced during pregnancy, with dysregulation of the ET system resulting in preeclampsia. Further research is necessary to elucidate the relative roles of the ET system in blood pressure control in both sexes and to further explore the potential benefits of pharmacological ET blockade in women.

Keywords: hypertension; preeclampsia; sex differences.

Publication types

  • Review

MeSH terms

  • Animals
  • Antihypertensive Agents / adverse effects
  • Blood Pressure* / drug effects
  • Endothelin Receptor Antagonists / adverse effects
  • Endothelins / metabolism*
  • Female
  • Humans
  • Hypertension / drug therapy
  • Hypertension / epidemiology
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • Male
  • Pre-Eclampsia / drug therapy
  • Pre-Eclampsia / metabolism
  • Pre-Eclampsia / physiopathology
  • Pregnancy
  • Receptors, Endothelin / drug effects
  • Receptors, Endothelin / metabolism
  • Risk Factors
  • Sex Factors
  • Signal Transduction
  • Treatment Outcome
  • Vasoconstriction* / drug effects

Substances

  • Antihypertensive Agents
  • Endothelin Receptor Antagonists
  • Endothelins
  • Receptors, Endothelin