Abstract 1829 Poster Session I, Saturday, 5/1 (poster 94)

Nitric oxide (NO) dilates the pulmonary circulation by increasing cGMP in lung vascular smooth muscle. Inhaled NO (iNO) is now the mainstay of treatment for persistent postnatal pulmonary hypertension. In severe lung disease, however, iNO sometimes fails to reduce pulmonary vascular resistance (PVR). We previously found that iNO decreased PVR in 7-12 old preterm lambs with evolving chronic lung disease (CLD), but not in 3 wk old preterm lambs with established CLD. This lack of response to iNO was attributed to reduced abundance of soluble guanylate cyclase in lung vascular smooth muscle. In these lambs with established CLD, iv infusion of 8-Br-cGMP caused a consistent 30-35% reduction of PVR. These lambs, however, were normoxemic and had only modest pulmonary hypertension. To see if cGMP might have a similar effect in lambs with more severe pulmonary hypertension from sustained hypoxemia, we mechanically ventilated four 3 wk old term lambs with 15% oxygen to induce steady-state hypoxic pulmonary vasoconstriction for 4-6h. The lambs had chronically implanted pulmonary arterial (pa) and left atrial (la) catheters for measurements of vascular pressures (P) and a Doppler flow probe around the main pulmonary artery for measurement of cardiac output (CO) before and during iv infusion of 8-Br-cGMP at 10, 50 and 150 (µg/min)kg during change with 10 or 50 (µg/min)/kg 8-Br-cGMP, but consistently decreased by 38% during 8-Br-cGMP infusion at 150 (µg/min)/kg. (Table)

Table 1 No caption available

This reduction in PVR persisted for at least 15 min after 8-Br-cGMP was stopped in the presence of sustained hypoxia. Systemic vascular resistance did not decrease significantly during iv infusion of 8-Br-cGMP. Together with our previous studies, these findings suggest that iv infusion of a cGMP analog relaxes lung vascular smooth muscle in lambs with pulmonary hypertension from either sustained hypoxia or CLD.