FUNCTIONAL ONTOGENY OF PULMONARY VASCULAR DA(1) DOPAMINE-RECEPTORS INTHE ISOLATED-PERFUSED RABBIT LUNG

Using an in situ isolated salt-perfused rabbit lung preparation, we in vestigated the functional ontogeny of pulmonary vascular dopamine rece ptors. In rabbits from 1 to 23 d of age, we measured pulmonary vascula r vasodilatory responses to the peripheral vascular dopamine receptor (DA(1)) agonist, fenoldopan, and sodium nitroprusside during prostagla ndin F-2 alpha-induced pulmonary vasoconstriction. In separate experim ents, the lungs were pretreated with the DA(1) receptor blocker, SCH 2 3390, before prostaglandin F-2 alpha, fenoldopam, and sodium nitroprus side. Lungs from rabbits at one of 6 age groups (n = 6-8 per group) we re ventilated and perfused. After a stabilization period, prostaglandi n F-2 alpha was infused into the pulmonary inflow catheter in a concen tration range to yield a sustained rise in mean pulmonary artery press ure (4.9 +/- 0.2 mm Hg). Fenoldopam was injected into the pulmonary ar tery at doses of 0.01, 0.1, 1.0, and 10 mu g/g after a recovery period , sodium nitroprusside (0.2 mu g/g) was injected into the pulmonary ar tery, and the resultant changes in vascular pressure were recorded. Ac ross all age groups, with and without DA(1) receptor blockade, sodium nitroprusside-induced vasodilation was similar (-2.7 +/- 0.2 mm Hg) an d was considered reference vasodilation. The fenoldopam vasodilation r esponse was considered a percentage of the sodium nitroprusside refere nce. Response to fenoldopam varied significantly (p < 0.05 by analysis of variance) across the six age groups, with a maximum at 3-5 d of ag e. Pretreatment with SCH 23390, a selective DA(1)-blocking agent, sign ificantly attenuated fenoldopam vasodilation in all but the youngest a nimals (age 0-2 d), in which no blockade effect was noted. We conclude that there are significant age-related changes in the vascular respon ses to fenoldopam. We speculate that endogenous dopamine and vascular dopamine receptors may play a role in mediating changes in the transit ional, pulmonary circulation.