The pulmonary vascular effects of three prostaglandin I2 analogs in conscious newborn lambs

JE Lock, F Coceani, F Hamilton, A Greenaway-Coates and PM Olley

Pulmonary and systemic vascular effects of three stable prostaglandin (PG) I2 analogs were studied in normoxic and hypoxic conscious newborn lambs. The three agents were : (5E)-6a-carba-PGI2 (analog I); 9-deoxy-9 alpha, 6-nitrilo-PGF1 hydrochloride (analog II); and (2E,5S)-9-deoxy- 5,9 alpha-epoxy-13,14-dihydro-delta 1-PGF1 (analog III). Each component was injected into either a branch pulmonary artery or the ascending aorta. Locally induced alterations in pulmonary vascular tone were assessed from changes in the ratio of blood flow to the injected lung over total flow (delta Qinj/Qt). Each compound was a systemic vasodilator, with thresholds from 1 to 3 micrograms/kg. However, analog III was without local pulmonary vasoactivity, and analog I was a pulmonary vasodilator only at the highest dose used (30 micrograms/kg) and in hypoxic lambs. Analog II, in contrast, was a pulmonary vasodilator in both hypoxic (threshold = 3 micrograms/kg) and normoxic (threshold = 10 micrograms/kg) lambs. Moreover, only analog II mimicked PGI2 during hypoxia by decreasing vascular resistance in the injected lung more than systemic resistance. These results demonstrate that PGI2 analogs are vasodilators with variable activity on the pulmonary and systemic circulations of the newborn lamb. Of the three analogs tested, only analog II resembles PGI2 in being more specific for the pulmonary as opposed to the systemic circulation. Analog II, however, is less active than PGI2 in this regard.

Volume 215, Issue 1, pp. 156-159, 10/01/1980
Copyright © 1980 by American Society for Pharmacology and Experimental Therapeutics