ABSTRACT
Angiotensin converting enzyme (ACE) inhibitors were evaluated from their effects on human arterial smooth muscle cells in culture. [3H]ramipril binding has been determined in two different cell lines exhibiting ACE(+) and ACE(-) phenotypes. Specific binding occurred only in ACE(+) cells, was saturable, and displayed a Kd of 1 nM with a beta max value of 3.5 fmol/10(6) cells. Ramipril specific binding did not significantly modulate PGI2 synthesis in ACE(+) cells. By contrast, ramipril and, to a lesser extent, captopril appeared as weak inhibitors of PGI2 synthesis in ACE(-) cells. These data indicate that human arterial SMCs may express several phenotypes of the renin-angiotensin system under culture conditions and that ACE inhibitors may exert a non-renin-angiotensin-mediated pharmacological effect on eicosanoid synthesis.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Muscle, Smooth, Vascular/drug effects , Renin-Angiotensin System/physiology , Cells, Cultured , Eicosanoids/biosynthesis , HumansABSTRACT
The capacity of arterial SMCs to produce PGI2 when stimulated by exogenous AA was studied in proliferative and confluent cultured cells and at different periods following endothelial denudation in vivo. PGI2 production per cell was doubled during the exponential growth-phase in culture. By contrast, increased PGI2 formation did not correlate with mitotic activity in intimal regeneration tissue but with the presence of SMCs in a synthetic phenotype. The present results suggest a potential role for PGI2 in SMC differentiation and proliferation.
Subject(s)
Epoprostenol/biosynthesis , Muscle, Smooth, Vascular/metabolism , Animals , Aorta/metabolism , Arachidonic Acid , Arachidonic Acids/metabolism , Cell Division , Cyclic AMP/analysis , In Vitro Techniques , Kinetics , Male , RabbitsSubject(s)
Cyclic AMP/physiology , Epoprostenol/biosynthesis , Muscle, Smooth, Vascular/metabolism , Adenylyl Cyclases/metabolism , Animals , Aorta, Thoracic , Arachidonic Acids/metabolism , Cells, Cultured , Cyclic AMP/metabolism , Cyclic GMP/metabolism , Feedback , Male , Prostaglandins/metabolism , Rats , Rats, Inbred StrainsABSTRACT
In addition to the well established cyclooxygenase pathway, cultured aortic smooth muscle cells convert arachidonic acid to several polar metabolites identified by high performance liquid chromatography and gaz chromatography-mass spectrometry. 15-Hydroxyeicosatetraenoic acid, 12-Hydroxyeicosatetraenoic acid and 5-Hydroxyeicosatetraenoic acid are the major products formed. These observations indicate that the rabbit aortic smooth muscle cells are a potential source of lipoxygenase products and raise the possibility that this pathway of arachidonic acid metabolism can influence the biological functions of arterial myocytes under normal and pathological conditions.
