eNOS expression is not altered in pulmonary vascular remodeling due to increased pulmonary blood flow

Congenital heart lesions resulting in increased pulmonary blood flow are common and if unrepaired often lead to pulmonary hypertension and heart failure. Therefore, we hypothesized that increased pulmonary blood flow without changes in pressure would result in remodeling of the pulmonary arterial wall. Furthermore, because the vasodilator nitric oxide is produced by the lung, is regulated by flow in the systemic circulation, and has been associated with the regulation of smooth muscle cell proliferation, we hypothesized that increased pulmonary blood flow would result in altered expression of endothelial nitric oxide synthase (eNOS). To study this hypothesis, 42-day-old Sprague-Dawley rats had creation of an aortocaval shunt to increase pulmonary blood flow for 6 wk. The shunt resulted in a significant increase in the heart-and lung-to-body weight ratios (>2-fold; P < 0.05) without significant alteration of pulmonary or systemic blood pressures. Significant thickening of the pulmonary arterial medial wall developed, with increased muscularization of small (50-100 mu m)- and medium (101-200 mu m)-sized arteries as evidenced by alpha-actin smooth muscle staining. Proliferating cell nuclear antigen staining and bromodeoxyuridine labeling did not detect proliferating smooth muscle cells in the vascular wall. eNOS Western and Northern blot analyses and immunohistochemical staining demonstrated that eNOS protein and mRNA levels were not altered in the shunt lungs compared with sham controls. Therefore, increased pulmonary flow without increased pressure resulted in pulmonary artery medial thickening, without ongoing proliferation. Unlike chronic hypoxia-induced vascular remodeling, the pulmonary vascular remodeling resulting from increased pulmonary blood flow is not associated with changes in eNOS.