Pregnant or not Pregnant—Systemic or Pulmonary Hypertension Induced by Thromboxane A₂ and Deficiency of Prostaglandins: A Hypothesis

Abstract

Background: Dysfunctional vascular endothelium with deficient production of prostacyclin (PGI₂), persistent activation of platelets, enhanced release of thromboxane A₂ (TXA₂), and vasospasm are common features of two vascular disorders, both of which are of unknown origin and affect exclusively or mainly women of childbearing age: preeclampsia (PE) and primary pulmonary hypertension (PPH). The association of high TXA₂/PGI₂ ratio with systemic hypertension in pregnant but with pulmonary hypertension in nonpregnant women is intriguing.

Hypothesis: Based on experimental data collected from intact nonpregnant and pregnant rabbits, isolated and perfused lung preparations, and TXA₂ receptor studies performed on pulmonary arterial membranes, we hypothesize that in the nonpregnant state the pulmonary resistance vessels may form the primary target site of TXA₂, and that during pregnancy the sensitivity of these vessels to TXA₂ may be blunted simultaneously with enhanced systemic vascular sensitivity to this eicosanoid. Such a reciprocal change of vascular TXA₂ sensitivity could explain the association of high TXA₂/PGI₂ ratio with PPH in nonpregnant women and with systemic hypertension n in pregnant women.