C-type natriuretic peptide (CNP) is a recently described endothelium-derived relaxing factor. CNP relaxes vascular smooth muscle and inhibits smooth muscle proliferation by binding to natriuretic peptide receptor (NPR) type B (NPR-B) and producing cGMP. Lung parenchyma and fifth-generation pulmonary arteries (PA) and veins (PV) were isolated from late-gestation fetal lambs. All three types of NPR mRNA were detected in PA and PV by RT-PCR. CNP and NPR-B immunostaining was positive in pulmonary vascular endothelium and medial smooth muscle. CNP concentration-response curves of PA and PV were compared with those of atrial natriuretic peptide (ANP) by use of standard tissue bath techniques. CNP relaxed PV significantly better than PA. ANP relaxed PA and PV equally, but ANP relaxed PA significantly better than CNP. Pretreating PA and PV with natriuretic peptide receptor blocker (HS-142-1) or cGMP-dependent protein kinase inhibitor Rp-beta-phenyl-1- N2-etheno-8-bromoguanosine 3',5'-cyclic monophosphorothionate significantly inhibited the CNP relaxation response, indicating that the response was mediated through the NPR-cGMP pathway. We conclude that CNP is important in mediating pulmonary venous tone in the fetus.

Background: Vascular segments in the fetal lung differ anatomically and functionally from one another. At birth, the nitric oxide (NO) pathway plays an integral role in reducing pulmonary vascular resistance through a marked vasodilation. However, the contributions of each vascular segment to this dilation are unclear. We sought to determine the distribution of soluble guanylate cyclase (sGC), the enzyme NO activates to induce vasodilation across the pulmonary vasculature. Methods: Pulmonary airspaces were expanded with freezing compound and the pulmonary arterial tree was infused with barium sulfate gelatin. Soluble guanylate cyclase was localized by immunohistochemistry across the pulmonary vasculature of four near-term fetal lambs and its immuno-reaction product was assessed by a semiquantitative method. The physi-ologic response of fourth-and fifth-generation arteries and veins isolated from age-matched lambs to NO was measured using standard tissue bath techniques. Results: Clear differences in sGC immunostaining were present throughout the pulmonary vasculature: very weak to absent in large arteries accompanying bronchi, but intensely positive for veins. This pronounced staining for sGC in preacinar veins correlated with a 100-fold greater sensitivity to NO in veins compared to arteries of the same generation. The percentage of arteries staining positively approached 100% at the level of respiratory bronchioles and alveoli. Conclusions: These findings suggest that the increased response to NO in preacinar veins compared to that of arteries is in part due to increased sGC within venous vascular smooth muscle. Furthermore, intense staining within distal arteries implies a greater role for NO-mediated vasodila-tion within these segments. Anat. The pulmonary vasculature of the fetus and the newborn is heterogeneous in structure and function. Anatomically, pulmonary arteries of the near-term fetus and newborn are classified or 'landmarked' according to the airway they accompany (Reid, 1984). The walls of large conduit arteries associated with the cartilagenous airways are thick and are composed of multilayered elastic lamellae (Reid, 1979) allowing the vessel to absorb the direct pressure of blood flow coming from the right ventricle. In the resistance segment of the pulmonary arterial tree that accompanies terminal bronchioles, the vessels contain a thick muscular me-dial layer. In the near-term fetus and through infancy, the precapillary arteriolar bed (at the level of respiratory bronchioles and alveoli) is comprised almost entirely of partially muscular or non-muscular vessels. With age, vessels of the precapillary segment become fully muscularized and in the adult extend to the capillary bed. Although pulmonary veins contain fully, partially, and non-muscular segments similar to those of arteries, the structure of veins differs from that of pulmonary arteries (Michel, 1982). At all stages of development, pulmonary veins are less muscular and have a smaller medial thickness than arteries of the

ABSTRACT:During the transition at birth to air breathing, regulation of surfactant release from alveolar type II (ATII) cells is critical. Atrial natriuretic peptide (ANP) stimulates natriuretic peptide receptor-A (NPR-A) and increases intracellular cGMP. We examined the changes in ANP and NPR-A in respiratory epithelium during the perinatal period using immunohistochemistry and studied the effect of ANP on surfactant release from ATII cells isolated from fetal and newborn lambs. NPR-A mRNA was detected in the fetal lung by Northern Blot and RT-PCR. At 100 d gestation (term 145 d), ANP staining was absent and NPR-A staining was weak in cuboidal epithelial cells. ANP and NPR-A staining was prominent in ATII cells at 136 d gestation and was undetectable postnatally. ANP stimulated (maximal effect at 10 Ϫ10 M) surfactant release from both late gestation fetal and neonatal ATII cells. Protein kinase G inhibition significantly blocked this release. We conclude that ANP stimulates surfactant release in isolated perinatal ATII cells by a cGMPdependent mechanism. ANP and NPR-A expression in ATII cells is greatest in late gestation and declines sharply postnatally. We speculate that increased activity of the ANP/NPR-A pathway in late gestation may prime the surfactant system, preparing the lung for air breathing. (Pediatr Res 63: 239-244, 2008)

Hidradenomas, also referred to as nodular hidradenomas or clear cell hidradenomas (CCH), are benign cutaneous eccrine tumors usually 2-3 cm in dimension. Hidradenomas are relatively common; however, giant forms are rare. We report a case of an 8.0 x 6.0 x 3.0 cm clear cell hidradenoma of the left knee in a 43-year-old man. The tumor was mobile, located above the patellar tendon and was without bony involvement on imaging studies. Grossly, the resected tumor was unencapsulated and tan, with a solid and cystic cut surface showing papillary excrescences on the cyst wall. Microscopically, the tumor cells showed an infiltrative growth pattern at the periphery, however, the tumor cytology was bland and no necrosis or mitoses were identified. The overlying dermis contained hemosiderin pigment deposition and infiltration with eosinophils. Immunohistochemically, tumor cells were positive for cytokeratin, CAM5.2, p53, carcino-embryonic antigen (CEA) and epithelial membrane antigen (EMA), and negative for CD10 and Ki-67. The cytological features of hidradenomas can present diagnostic challenges, as other 'clear cell' tumors such as metastatic renal cell carcinoma should be considered. Immunohistochemical studies and differential diagnoses are discussed.

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