PT - JOURNAL ARTICLE AU - P J Kadowitz AU - P D Joiner AU - A L Hyman AU - W J George TI - Influence of prostaglandins E1 and F2alpha on pulmonary vascular resistance, isolated lobar vessels and cyclic nucleotide levels. DP - 1975 Mar 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 677--687 VI - 192 IP - 3 4099 - http://jpet.aspetjournals.org/content/192/3/677.short 4100 - http://jpet.aspetjournals.org/content/192/3/677.full SO - J Pharmacol Exp Ther1975 Mar 01; 192 AB - The effects of prostaglandins E1 (PGE1) and F2alpha) on the pulmonary vascular bed were studied in the intact dog under conditions of controlled pulmonary blood flow. PGF2alpha increased lobar arterial and venous pressure when injected or infused into the lobar, artery. The pressor response was dose-related and doses as low as 0.03 and 0.1 mug, which established concentrations of 0.1 to 0.3 ng/ml in lobar arterial blood, increased pulmonary vascular resistance. PGF2alpha also increased airway resistance in the left lower lobe. However, the effects of this substance on the vascular bed were not related to its effects on bronchomotor tone since similar pressor responses were observed in normal and nonrespiring lobes, PGE1 decreased pressure in the lobar artery and vein when infused into the lobar artery and the effects of PGE1 and PGF2alpha on the pulmonary vascular bed were similar when the lung was perfused with dextran or with blood. PGF2alpha increased isometric tension in isolated helical segments of lobar vein 3 to 5 mm in diameter but was without effect on arterial segments of the same diameter. The increase in isometric tension in the venous segments with PGF2alpha was associated with a significant increase in intracellular levels of guanosine 3',5'-monophosphate (cGMP) but no change in adenosine 3',5'-monophosphate (cAMP) levels. PGE1 decreased isometric tension in both arterial and venous segments and the decrease in tension was accompanied by a significant elevation in smooth muscle cAMP levels and a small but significant reduction in vein cGMP. Results of the present study indicate that PGF2alpha increases pulmonary resistance by constricting lobar veins and to a lesser extent vessels upstream in the precapillary bed whereas PGE1 dilates lobar veins and upstream vessels. These results suggest that PGE1-induced vasodilation may be mediated by an increase in cAMP levels while PGF2alpha-induced venoconstriction may be related to increased smooth muscle levels of cGMP.