Salt-sensitive hypertension and reduced fertility in mice lacking the prostaglandin EP2 receptor

Nat Med. 1999 Feb;5(2):217-20. doi: 10.1038/5583.


Prostaglandins (PGs) are ubiquitous lipid mediators derived from cyclooxygenase metabolism of arachidonic acid that exert a broad range of physiologic activities, including modulation of inflammation, ovulation and arterial blood pressure. PGE2, a chief cyclooxygenase product, modulates blood pressure and fertility, although the specific G protein-coupled receptors mediating these effects remain poorly defined. To evaluate the physiologic role of the PGE2 EP2 receptor subtype, we created mice with targeted disruption of this gene (EP2-/-). EP2-/- mice develop normally but produce small litters and have slightly elevated baseline systolic blood pressure. In EP2-/- mice, the characteristic hypotensive effect of intravenous PGE2 infusion was absent; PGE2 infusion instead produced hypertension. When fed a diet high in salt, the EP2-/- mice developed profound systolic hypertension, whereas wild-type mice showed no change in systolic blood pressure. Analysis of wild-type and EP2-/- mice on day 5 of pregnancy indicated that the reduced litter size of EP2-/- mice is due to a pre-implantation defect. This reduction of implanted embryos could be accounted for by impaired ovulation and dramatic reductions in fertilization observed on day 2 of pregnancy. These data demonstrate that the EP2 receptor mediates arterial dilatation, salt-sensitive hypertension, and also plays an essential part in female fertility.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blastocyst
  • Cloning, Molecular
  • Embryonic Development
  • Female
  • Hypertension / complications*
  • Hypertension / etiology
  • Infertility, Female / etiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pregnancy
  • Receptors, Prostaglandin E / genetics
  • Receptors, Prostaglandin E / physiology*
  • Receptors, Prostaglandin E, EP2 Subtype
  • Sodium, Dietary / adverse effects
  • Vasodilation


  • Ptger2 protein, mouse
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP2 Subtype
  • Sodium, Dietary