Characterization of thromboxane and prostacyclin effects on pulmonary vascular resistance.
Although thromboxane and prostacyclin (PGI2) have long been described as major controllers of pulmonary vascular resistance, little has been reported on the characteristics of the interactions between the two arachidonic acid products. The current study uses segmental vascular resistance and compliance measurements to evaluate the actions of thromboxane and PGI2 in isolated blood-perfused rat lung. The thromboxane analogue U-46619 increases pulmonary vascular resistance by increasing only small artery resistance and decreases pulmonary vascular compliance in the middle compartment. Among the vascular effects of U-46619 are a maximum increase in resistance (RmaxU-46619) of 60.3 +/- 15.6 cmH2O.l-1.min.100 g-1 and a concentration required for 50% of maximum increase (K0.5,U-46619) of 1.60 +/- 0.85 nM for small artery resistance, a minimum vascular compliance (CminU-46619) of -0.93 +/- 0.58 cmH2O, and a K0.5,U-46619 of 1.10 +/- 1.60 nM for middle compartment compliance. Similar results were obtained for total resistance and total compliance. The effects of PGI2 on thromboxane-induced resistance and compliance changes were evaluated using K0.5,PGI2, RmaxPGI2, and CmaxPGI2 at each dose of thromboxane. PGI2 was more effective in reversing the thromboxane constriction at higher concentrations of thromboxane. These data show that the absolute concentration of PGI2 and thromboxane and not a simple ratio of thromboxane to PGI2 determines vascular tone.
Barnard
J W
JW
Department of Physiology, College of Medicine, University of South Alabama, Mobile 36688.
Ward
R A
RA
Adkins
W K
WK
Taylor
A E
AE
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism; D017482:Receptors, Thromboxane; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011464:Epoprostenol