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High levels of circulating catecholamines are found in the fetus, and fetal stress and birth induce a marked surge in catecholamine secretion. Little is known about the role of catecholamines on the fetal pulmonary circulation. To determine the effects of catecholamines on the pulmonary vascular tone, we tested the hemodynamic response to norepinephrine and dopamine infusion in chronically prepared late-gestation fetal lambs. We found that norepinephrine infusion (0.5 microg. kg(-1). min(-1)) increased pulmonary artery pressure (PAP) by 10 +/- 1% (P < 0.01), left pulmonary artery blood flow by 73 +/- 14% (P < 0.01), and decreased pulmonary vascular resistance (PVR) by 33 +/- 6% (P < 0.01). The pulmonary vasodilator effect of norepinephrine was abolished after nitric oxide synthase inhibition. Dopamine infusion at 5 microg. kg(-1). min(-1) did not significantly change PVR. Conversely, dopamine infusion at 10 microg. kg(-1). min(-1) increased PAP (P < 0.01) and progressively increased PVR by 30 +/- 14% (P < 0.01). These results indicate that catecholamines may modulate basal pulmonary vascular tone in the ovine fetus. We speculate that catecholamines may play a significant role in the maintenance of the fetal pulmonary circulation and in mediating changes in the transitional pulmonary circulation.

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Recent in vitro studies reported that nitric oxide release and pulmonary vasorelaxation can be mediated by endothelial ␣ 2 -adrenoceptor activation. As norepinephrine (␣ 1 -,␣ 2 -, and ␤ 1 -adrenoceptor agonist) was found to induce pulmonary vasodilation in the ovine fetus, we hypothesized that ␣ 2 -adrenoceptors may modulate basal pulmonary vascular tone and mediate the vascular effect of norepinephrine during fetal life. To determine the role of ␣ 2 -adrenoceptors and the mechanisms of norepinephrine-mediated vasodilation in the fetal pulmonary circulation, we tested, in chronically prepared late-gestation fetal lambs, the hemodynamic response to 1) yohimbine (␣ 2 antagonist); 2) UK 14,304 (␣ 2 agonist) with and without L-nitro-arginine (nitric oxide synthase inhibitor); and 3) norepinephrine infusion with and without yohimbine. We found that yohimbine increased mean pulmonary artery pressure by 15% (p Ͻ 0.05), decreased pulmonary flow by 22% (p Ͻ 0.01), and increased pulmonary vascular resistance by 51% (p Ͻ 0.01). UK 14,304 increased pulmonary flow by 145% (p Ͻ 0.01) and decreased pulmonary vascular resistance by 58% (p Ͻ 0.01). L-Nitro-arginine abolished the UK 14,304-mediated pulmonary vasodilation. Norepinephrine (0.5 g·kg Ϫ1 ·min Ϫ1 ) increased both pulmonary flow by 61% (p Ͻ 0.01) and pulmonary arterial pressure by 13% (p Ͻ 0.01) and decreased pulmonary vascular resistance by 33% (p Ͻ 0.01). Yohimbine abolished the norepinephrine-induced pulmonary vasodilation. This study suggests that 1) a basal ␣ 2 -adrenoceptor activation-induced pulmonary vasodilation exists during fetal life; 2) the pulmonary vascular effects of ␣ 2 -adrenoceptor activation are related at least in part to nitric oxide production; and 3) the norepinephrine-mediated pulmonary vasodilation involves ␣ 2 -adrenoceptor activation. As a surge of norepinephrine exists at birth, we speculate that norepinephrine and endothelial ␣ 2 -adrenoceptor activation may play a significant role in pulmonary vasodilation at birth. High resistance and low blood flow characterize the fetal pulmonary circulation. PVR decreases dramatically during the normal transition from the fetal to neonatal circulation at birth. Three main factors contribute to the increase of Q p during this transition: ventilation of the lung (1), increased O 2 (2), and hemodynamic forces, such as increased shear stress (3). Vasoactive mediators released from the endothelium, such as NO, play a major role in the regulation of acute changes in vascular tone in the perinatal lung, and in many cases, modulate the pulmonary vascular response to these birth-related stimuli (4). Inhibition of NO synthesis can attenuate the postnatal adaptation of the pulmonary circulation (5). The vasodilator action of several substances, such as acetylcholine, bradykinin, or ADP, and shear stress are dependent, at least in part, on NO release (6). More recently, in vitro studies reported that NO release and pulmonary vasorelaxation can also be mediated by endothelial ␣ 2 -adrenoceptor activation (7-9). Ho...