Differential changes in endothelin-1 and endothelial nitric oxide synthase gene expression in rats with a chronic high pulmonary flow.

The expressions of endothelin-1 (ET-1) and endothelial nitric oxide synthase were assessed in the lung of adult Wistar rats (n = 6/group) undergoing an abdominal aortocaval shunt to increase pulmonary blood flow for 4, 8 or 12 weeks. The shunt resulted in significant medial hypertrophy of the pulmonary artery without significant increases in pulmonary and systemic arterial pressure. A competitive reverse transcriptase-polymerase chain reaction demonstrated significant increases in pulmonary preproET-1 mRNA at 12 weeks (mean +/- standard error of the mean; shunt, 1.82 +/- 0.12; sham, 1.00 +/- 0.15; P < 0.05) and in pulmonary endothelial nitric oxide synthase mRNA at both 8 weeks (shunt, 1.57 +/- 0.12; sham, 1.00 +/- 0.18; P < 0.05) and 12 weeks (shunt, 1.89 +/- 0.18; sham, 1.00 +/- 0.13; P < 0.05). In addition, western blot analysis showed increases in pulmonary endothelial nitric oxide synthase protein by 126% and 164% at 8 and 12 weeks, respectively, in the shunt animals. However, the plasma ET-1 concentrations and the lung ET-1 contents were unchanged. These results indicate that endothelial nitric oxide synthase gene expression was upregulated, prior to that of ET-1, at the transcriptional level during pulmonary vascular remodeling in this chronic shunt model.