The purpose of these studies was to examine cardiovascular responses to fourth cerebral ventricle (4V) administration of nitroglycerin (NTG) or an inhibitor of nitric oxide (NO) synthesis in the near-term ovine and determine if, during birth, neuronal NO synthase (nNOS) is induced in noradrenergic A1 neurons in the medial nucleus tractus solitarius (mNTS). In chronically instrumented fetal sheep, 4V injection of NTG (1.2 nmol), an NO donor, produced an arterial blood depressor and a moderate decrease in heart rate. Arterial blood pressure (ABP) is increased by 4V administration of N^G-nitro-L-arginine methyl ester (L-NAME, 10 nmnol), an inhibitor of NO synthesis, in fetuses. Sections of the medulla from fetuses and newborn lambs were examined by using immunolabeling with tyrosine hydroxylase (TH) antibody combined with NADPH diaphorase (NADPHd) histochemistry, a marker of nNOS activity. The NADPHd positive cells and TH positive cells containing NADPHd reactivity were significantly increased in the mNTS of newborn compared to the fetus. The results suggest that during birth there is up-regulation of NADPHd/nNOS in the noradrenergic neurons of mNTS resulting in a centrally mediated reduction of fetal ABP.