Abstract

Prostaglandin F_2α (PGF_2α), unlike most other prostaglandins, is pressor in rats and dogs. The present investigation was undertaken to determine the mechanism of the pressor activity of this naturally occurring substance. The pressor activity in rats persisted after ganglion blockade or reserpine pretreatment, so it is neither mediated over the conventional sympathetic nervous system nor due to release of catecholamines from peripheral nerve endings. Administration of PGF_2α into the perfused limb of the dog prepared for analysis of segmental vascular pressures demonstrated that the pressor activity resulted, at least in part, from an increase in peripheral resistance, and that the increase in resistance occurred primarily in the venous segment. In unanesthetized, trained dogs prepared with electromagnetic flow-probes, PGF_2α increased both cardiac output and systemic blood pressure, leaving calculated total peripheral resistance virtually unchanged. The increase in cardiac output was not caused by a direct effect of the agent on myocardial contractility, as was demonstrated in anesthetized dogs prepared with a Walton-Brodie strain gauge arch. Further evidence that the pressor activity of PGF_2α is primarily the result of venoconstriction was obtained from experiments in which a perfusion pump was used to by-pass the right heart and a constant pressure stabilizing reservoir was placed in the venous return. In this preparation PGF_2α consistently caused an increase in reservoir volume and a marked increase in pulmonary resistance. The possible role of a substance with properties similar to those of PGF_2α in the etiology of hypertension is discussed.