Endothelial prostacyclin production, synergistic effect between adrenergic stimulating and blocking drugs.
Endothelial cells (EC) produce prostacyclin (PGI2) in high quantities which at the luminal surface decreases platelet aggregation and adhesion and basal to the cell relaxes smooth muscle cells (SMC). Connections have been reported between prostacyclin production, hypertension and the degree of adrenergic activation. The present study tested the hypothesis that prostacyclin production by EC could be regulated by adrenergic mechanisms. EC were isolated from human umbilical cord veins. Washed cells were seeded and grown to confluency on tissue culture dishes. The test drugs were simultaneously added to parallel dishes. Samples were collected from the conditioned medium and analyzed for 6-keto-PGF1a with RIA technique. Endothelial cells pretreated with the betaadrenoceptor blocking drugs metoprolol or propranolol synergistically increased basal prostacyclin production when exposed to betaadrenergic stimulation. However, using isomers with high or low betaadrenoblocking effect, this synergism was demonstrated not to be associated to the betaadrenoceptor blocking effect of the drugs per se. These findings may have implications on the arterial hypertensive state characterized by high sympathetic tonus and low PGI2 production. The data may offer an explanation why hypertensive individuals react with increased PGI2 production, upon betaadrenoceptor blocking therapy.
Rydholm
H
H
Department of Surgery, Ostra Hospital, University of Göteborg, Sweden.
Boström
S
S
Hansson
G
G
Risberg
B
B
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000322:Adrenergic Agonists / Q000494:pharmacology*; D018674:Adrenergic Antagonists / Q000494:pharmacology*; D002478:Cells, Cultured; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008790:Metoprolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D014471:Umbilical Veins
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D015121:6-Ketoprostaglandin F1 alpha; D011433:Propranolol; D011464:Epoprostenol; D008790:Metoprolol; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine