BACKGROUND To elucidate the pathophysiological significance of endothelin in pulmonary hypertension associated with congenital heart defects, we measured plasma endothelin-like immunoreactivity (ET-LI) concentrations by using radioimmunoassay in 18 patients with pulmonary hypertension (PH group; age, 6 months to 12 years) in comparison with 27 patients without pulmonary hypertension (non-PH group; age, 6 months to 12 years). METHODS AND RESULTS Blood samples were obtained from the vena cava, right atrium, right ventricle, left or right pulmonary artery, and pulmonary vein or the pulmonary arterial wedge position (pulmonary venous blood) during cardiac catheterization. Plasma ET-LI concentrations in the PH group were significantly higher than those in the non-PH group at all sampling sites. In the PH group, plasma ET-LI concentration showed a significant increase between the right ventricle and pulmonary artery and between the pulmonary artery and pulmonary vein. The increment of plasma ET-LI concentrations from the right ventricle to the pulmonary vein was significantly larger in the PH group than in the non-PH group and was significantly correlated with pulmonary artery pressure. CONCLUSIONS Plasma ET-LI concentrations were elevated in patients with pulmonary hypertension; the elevation was due to the increased production of ET-LI in pulmonary circulation, indicating the possible involvement of endothelin in the pathophysiology of pulmonary hypertension.

We compared 1.5 T magnetic resonance (MR) image findings with hypothalamic-pituitary function in 11 patients with idiopathic pituitary dwarfism, each of whom had a history of perinatal abnormalities, and 1 patient with posttraumatic pituitary dwarfism. MR imaging revealed transection of the pituitary stalk in all patients and the formation of an ectopic posterior lobe at the proximal stump in 9 patients, none of whom had polydipsia or polyuria. Three patients without an ectopic posterior lobe had diabetes insipidus. The 5 patients who had small pituitary glands (less than 2 mm in height) had hypothyroidism with low serum TSH concentrations and low serum cortisol responses to insulin-induced hypoglycemia; however, 7 patients with normal-sized pituitary glands had normal thyroid and adrenal function. The serum GH response to GHRH did not correlate with the size of the pituitary gland. The patients with small pituitary glands had delayed or prolonged serum TSH responses to TRH and impaired serum LH and FSH responses to GnRH; 4 of the patients with normal-sized pituitary glands had normal serum TSH, LH, and FSH responses. Only 2 patients had high basal serum PRL concentrations. The endocrinological data suggest that reestablishment of the hypothalamo-hypophyseal portal circulation, which cannot be seen by MR imaging, may occur. We suggest that the primary cause of idiopathic pituitary dwarfism in many patients is injury to the pituitary stalk at birth.

No abstract

ABSTRACI'. We evaluated the neuroprotective effect of lium in the conversion of L-arginine to L-citrulline by the enzyme the nitric oxide synthesis inhibitor, NC-nitro-L-arginine in NO synthase ( 9 , whose activity has also been reported in forea neonatal hypoxic-ischemic rat model. Unilateral hypoxic-brain homogenates (6). NMDA stimulates NO synthesis (7), and ischemic iqjury was produced in the brain of 7-dsld rats NO mediates glutamate neurotoxicity in vitro (8). NOARG, an using a combition of a common carotid artery ligation analog of L-arginine, competitively inhibits the enzymatic forand a hypoxic (8% oxygen) exposure for 2.5 h. In our mation of NO both in cultured endothelial cells (9) and cerebellar experimental condition, rectal temperatures did not differ homogenates (lo), also prevents neurotoxicity induced by between NC-nitro-L-argininetreated and salineinjected NMDA in cortical cultures (8), and easily crosses the blood-brain pups. We killed the animals 72 h later and assessed the barrier (10). hypoxic-ischemic brain damage histologically. NG-nitro-L-Contradictory reports concerning the possible neuroprotective 9 nine (2 mg/kg) administered intraperitoneally 1.5 h effect of NO synthesis inhibitors in adult models (1 1-16) be ore hypoxia resulted in 77% reduction of the infarcted prompted us to investigate whether NO was related to the genesis hemispheric volume and 87% reduction of the infarcted of cerebral hypoxic-ischemic brain damage in neonates. Sevenstriatal volume compared to saline injected controls. P -d-old rats were subjected to unilateral carotid artery ligation nitro-L-arginine given 1.5 h before the insult also signifi-followed by hypoxic exposure. This neonatal rat model shows cantly prevented hypoxic-ischemic damage in the five hip-infarction of the cerebral hemisphere ipsilateral to the carotid pocrunpal structures examined, dentate gyruq CA4, CA3, artery ligation (17), and has been frequently used to investigate CAI, and subiculum. NG-nitro-L-arginine administered im-the pathogenesis of cerebral hypoxia ischemia (for review see mediately after hypoxia did not prevent hypoxic-ischemic Refs. 1 and 18). We investigated the neuroprotective effect of brain damage. These results indicate that nitric oxide plays NOARG administered before and after a hypoxic insult. a key role in producing neonatal hypoxic-ischemic brain damage. (Pediatr RPS 35: 10-14,1994) MATERIALS AND METHODS AbbreviationsWe used the method of Rice et al. (17) to produce hypoxicischemic brain damage in neonatal rats. On the day of surgery, NMDA, N-methyl-aspa art ate 7-d-old Std:Wister rat (Japan SLC, Inc.) littermates (the day of NO, nitric oxide birth is defined as d 1) were paired according to sex and body NOARC, NC-nitro-L-arginine weight (f0.5 g), each pair consisting of a pup assigned to NOARG treatment and a saline-injected control. If one member of a pair died, the other member was discarded. Under ether anesthesia, the left carotid artery was exposed through a midline neck incision, doubly ligated, and severed b...