Vertebrate lungs: structure, topography and mechanics. A comparative perspective of the progressive integration of respiratory system, locomotor apparatus and ontogenetic development.

Vertebrate lungs are highly diverse in their structure, topographical position, ventilation mechanisms, constructional integration into the locomotor apparatus, and the interrelationships with the mode of their ontogenetic development. Vertebrate lungs evolved as supplementary air-breathing organs in primary fishes, being ventilated by buccal pumping. In most recent fishes the lungs are transformed into the hydrostatic swimbladder. This basic type of unicameral lungs and their buccal pumping ventilation are also found in recent amphibians. Land vertebrates developed a very efficient aspiration type of ventilation. In most recent reptiles the lungs are subdivided into three rows of lung chambers, enlarging the exchange surface in correlation to their increasing metabolic needs. The avian respiratory apparatus, with its volume-constant lungs and highly compliant air sacs, and the mammalian broncho-alveolar lung, with its very low compliance, are both derived from multicameral lungs. The avian and the mammalian respiratory systems are integrated very differently with the specific constructions of their locomotor apparatusses and the specific mode of their ontogenetic development.

Cell-specific nitric oxide synthase-isoenzyme expression and regulation in response to endotoxin in intact rat lungs.

Nitric oxide (NO) produced by NO synthase (NOS) serves as a ubiquitous mediator molecule involved in many physiologic lung functions, including regulation of vascular and bronchial tone, immunocompetence, and neuronal signaling. On the other hand, excessive and inappropriate NO synthesis in inflammation and sepsis has been implicated in vascular abnormalities and cell injury. At least three different NOS isoforms (neuronal/brain [bNOS], inducible [iNOS], and endothelial [eNOS]) have been described, which are all expressed in normal lung tissue. We investigated the cell-specific expression of bNOS, iNOS, and eNOS in perfused control rat lungs and lungs undergoing stimulation with endotoxin in the presence and absence of plasma constituents. Lung immunohistochemistry and quantitative evaluation of staining intensity showed endotoxin-induced increase in iNOS expression in particular in bronchial epithelial cells, cells of the bronchus-associated lymphoid tissue (BALT), alveolar macrophages, and vascular smooth muscle cells in a time- and dose-dependent fashion. In endothelial cells, which did not express iNOS at baseline, newly induced iNOS was found in response to endotoxin. In contrast, expression of eNOS was markedly suppressed under endotoxin challenge, particularly in bronchial epithelium, BALT, and alveolar macrophages but also in vascular smooth muscle cells and endothelial cells. eNOS expression in bronchial smooth muscle cells was not altered. In contrast to iNOS and eNOS, cellular expression of bNOS in epithelial cells, nerve fibers, BALT, and endothelial cells did not change in response to endotoxin. All changes in NOS regulation were found to be independent of plasma constituents. We conclude that endotoxin exerts a profound impact on the cell-specific NOS regulation in a large number of lung cell types. Prominent features include de novo synthesis or up-regulation of iNOS, in contrast to down-regulation of eNOS, which may well contribute to vascular abnormalities, inflammatory sequelae, and loss of physiologic functions in septic lung failure.