ZK 36–374, a stable analog of prostacyclin, prevents acute hypoxic pulmonary hypertension in the dog

Stephen L. Archer, Elliot Chesler, Jay N. Cohn, E. Kenneth Weir

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Vasodilator therapy in pulmonary hypertension is limited by the lack of an agent selective for the pulmonary circulation. The effects of intravenous prostacyclin and two stable prostaglandin analogs, ZK 36-374 and CL 115,347, were assessed on the preconstricted pulmonary vasculature of the anesthetized dog. During hypoxic vasoconstriction ZK 36–374 (0.4 fig/kg per min) markedly reduced pulmonary artery pressure (26 ± 3 to 13 ± 1 mm Hg) (p < 0.05) and pulmonary vascular resistance (6.2 ± 1.1 to 2.8 ± 0.2 mm Hg/liter per min) (p < 0.01). There was no significant effect on cardiac output, aortic pressure or arterial blood gases. Pulmonary vasoconstriction induced by prostaglandin F2a was similarly affected by ZK 36–374, and in this instance the aortic pressure was also reduced (158 ± 11 to 129 ± 11 mm Hg) (p < 0.01). ZK 36–374 (0.2 jttg/kg per min) was more effective in lowering hypoxic pulmonary vascular resistance (from 6.5 ± 0.6 to 3.0 ± 0.3 mm Hg/liter per min) than was prostacyclin (0.75 /xg/kg per min) (from 6.3 ± 0.6 to 4.2 ± 0.4 mm Hg/liter per min) (p < 0.05) and resulted in a smaller fall in aortic pressure (p < 0.05). CL 115,347 (1.0 /xg/kg per min) had no effect on the pulmonary vasculature during normoxia or when preconstricted by prostaglandin F2a or hypoxia, but reduced aortic pressure and total systemic resistance (p < 0.05). It appears to be a selective systemic vasodilator with no pulmonary vascular activity. ZK 36-374 is an effective agent in reversing pulmonary vasoconstriction in this model and has potentially useful selectivity for the pulmonary circulation. Oral administration is possible.

Original languageEnglish (US)
Pages (from-to)1189-1194
Number of pages6
JournalJournal of the American College of Cardiology
Volume8
Issue number5
DOIs
StatePublished - Jan 1 1986

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