Responses of pulmonary and systemic circulations of perinatal goats to prostaglandin F_2α

Abstract

The effects of exogenous prostaglandin (PG) F2α, as well as PGF1α and the 15-keto metabolites of both prostaglandins, upon unventilated fetal, premature newborn, and mature newborn goat pulmonary and systemic circulations were examined by infusing the compounds into the pulmonary circulation. PGF2α is a powerful pressor agent in both pulmonary and systemic circulations of fetal and neonatal goats. Broncho–pulmonary constriction was also observed in ventilated animals at infusion rates in excess of the lung's ability to catabolize the prostaglandin. The pressor effects were not attenuated by alpha-adrenergic blockade. PGF1α is qualitatively similar, but quantitatively less, in its effect. The 15-keto metabolites did not alter pulmonary or systemic circulation even at very high doses. The PGF2α threshold dose for increasing pulmonary vascular resistance is lowest in the unventilated fetus, greatest in the premature newborn, and intermediate in the newborn older than 1 day of age. The lower sensitivity of the pulmonary circulation to the exogenous vasoconstrictor in the immediate postventilation period suggests the presence of endogenous dilator activity. Since the increase in pulmonary vascular resistance produced by indomethacin is greatest in the newly ventilated fetus, less in the older newborn, and negligible in the unventilated fetus, the substance(s) responsible for the endogenous dilator activity would appear to require prostaglandin fatty acid cyclooxygenase activity for production.

Age-Dependent Effects of Indomethacin on Hypoxic Vasoconstriction in Neonatal Lamb Lungs

“…At comparable doses of arachidonic acid, newborn lambs showed a greater increase in PVR than in ventilaged fetal lambs (36). Also, mature newborn goats were more sensitive to PGF2, than premature newborn goats (37).…”

“…The concentrations of 6-keto-PGF,, were not different in the two age groups at any level of O2 (Table 2). Despite this, prostacyclin could still be responsible for an agedependent effect of indomethacin if the response of the pulmonary vasculature to PG12 varied with age in a fashion analagous to responses to arachidonic acid (36) and PGF2, (37). At comparable doses of arachidonic acid, newborn lambs showed a greater increase in PVR than in ventilaged fetal lambs (36).…”

Persistent pulmonary hypertension of the newborn.

“…The prostaglandin products of arachidonic acid metabolism, prostaglandin F 2 cx: and thromboxane A 2 are synthesized by the fetal lung (79,80) and are pulmonary vasoconstrictors in the fetal and newborn lung (81,82). However, infusion of the metabolite PGH 2 , which is intermediate between arachidonic acid and these prostaglandins, dilates the fetal pulmonary circulation (83), and blocking prostaglandin or thromboxane synthesis does not decrease resistance (84)(85)(86).…”

“…Prostacyclin (PGI 2 ) is synthesized primarily by endothelial cells, and it appears to have its smooth-muscle-relaxing effects via the production of cAMP. Prostacyclin and its metabolites 6-keto-PGfiCX: or 6-keto-PGE 1 are fetal pulmonary vasodilators that are more potent than PGE 2 (82,95,96).…”

Neural and Endocrine Regulation of Circulation in the Fetus and Newborn

“…Although PGFI, and PGR, (217) are vasoconstrictors, the pulmonary pressor response is not abolished by a-adrenergic block (209). The 15keto metabolites are less effective than the parent compounds.…”