BQ123, a selective ETA receptor antagonist, inhibited ET-1-induced growth of human pulmonary artery smooth muscle cells, indicating ET-1 acts as a co-mitogen via the ETA receptor.
Does BQ123 inhibit ET-1-mediated proliferation in human pulmonary artery smooth muscle cells?
ET-1 promotes proliferation of human pulmonary artery smooth muscle cells via the ETA receptor, an effect that can be inhibited by the selective antagonist BQ123.
Endothelin (ET-1) has been shown to be co-mitogenic for vascular smooth muscle cells (SMC) from human systemic arteries. A more modest growth-promoting effect has also been described in SMC from the bovine and porcine pulmonary circulation. Whether ET-1 has mitogenic properties in the human pulmonary circulation, and which ET receptor subtype mediates this response, is unknown. We first examined the effects of ET-1, ET-3, and the selective ETB agonist, Sarafotoxin 6c, on human pulmonary artery SMC growth. Cells were harvested from normal lung transplant donors. Growth was assessed by change in cell number 3 days after stimulation of quiescent cells. ET-1 in the presence of 0.3% serum produced a dose-dependent increase (82 +/- 1.5%) in cell number (threshold, 10(-11) M; maximal, 10(-7) M). ET-3 also stimulated growth (36 +/- 3.8%) but was less potent than ET-1 (threshold, 10(-9) M; maximal, 10(-7) M). The ETB selective agonist Sarafotoxin 6c had no proliferative effect. The effects of BQ123, a selective ETA receptor antagonist, on ET-1-induced growth were then assessed. BQ123 inhibited (threshold, 1.5 x 10(-7) M; maximal, 1.5 x 10(-5) M) ET-1-induced growth but had no effect on proliferation stimulated by the non-ET receptor-mediated growth factors, platelet-derived growth factor BB and 5-hydroxytryptamine. These results suggest that ET-1 is a potent co-mitogen for human proximal pulmonary artery SMC and that this effect is transduced by selective activation of the ETA receptor.
Zamora et al. (Fri,) conducted a other in Pulmonary artery smooth muscle cell proliferation. BQ123 (ETA receptor antagonist) vs. ET-1 alone, PDGF-BB, 5-hydroxytryptamine was evaluated on Cell growth assessed by change in cell number. BQ123, a selective ETA receptor antagonist, inhibited ET-1-induced growth of human pulmonary artery smooth muscle cells, indicating ET-1 acts as a co-mitogen via the ETA receptor.