Exposure to hypoxia for four days resulted in a significant incre

Exposure to hypoxia for four days resulted in a significant increase in proliferative activity by 34% in untreated ani mals and by 43% in vehicle injected mice. Administration of rapamycin completely abolished the hypoxia induced increase in proliferation. The anti prolif erative selleck products effect of rapamycin was restricted to hypoxia induced proliferation In mice housed at normoxia the number of Ki67 positive cells/vessel was not significantly changed by rapamycin compared to the untreated and the vehicle injected control animals, implying that rapamycin did not interfere with basal proliferative activity. Since proliferative activity had subsided after 3 weeks of exposure to hypoxia, no effect of rapamycin was detectable after this time period. Three weeks of hypoxia, however, induced a distinct increase in muscularization of intrapulmonary vessels.

The extent of muscularization rose Inhibitors,Modulators,Libraries about 53% both in untreated and vehicle injected mice. Whereas under normoxic conditions the degree of muscularization was unchanged by rapamycin administration, in lungs of hypoxic mice a 26% reduction of the muscularization was Inhibitors,Modulators,Libraries detectable. The rapamycin treated group did not differ significantly from animals housed at normoxia. Allocation of the distal arteries on one of five classes of vessel caliber ranging from 0 to 70m revealed that hypoxia induced a distinct shift towards ves sels with smaller calibers The relative proportion of arter ies with diameters smaller than 20m was approximately twice as high in mice kept for three weeks at hypobaric hypoxia in comparison to normobaric control animals.

The relative proportion of vessels with diameters between 20 and 30m was comparable Inhibitors,Modulators,Libraries in the normoxic and hypoxic groups. Accordingly, the relative proportion of vessel calibers of 30. 1 to Inhibitors,Modulators,Libraries 40m as well as 40. 1 to 50m was less in hypoxic mice. The relative proportion of ves sels with large diameters was not different in mice housed at normoxia or hypoxia. Rapamycin treat ment of mice did not affect the distribution of the vessels to the five caliber classes. carboxymethylcellulose Inhibitors,Modulators,Libraries muscularization intrapulmonary Proliferative activity and muscularization of intrapulmonary vessels of untreated mice and of animals injected with 0. 2% carboxymethylcellulose as vehicle or with rapamycin. Mice were kept for four days or three weeks at normoxia or at hypobaric hypoxia.

In frozen lung sections stained with anti Ki67 and anti smooth muscle actin the number of pro liferating cells per cross section of a vessel was quantified. The extent of muscularization of intrapulmonary arter ies was quantified by computer aided planimetry. The results right are given as boxplots. Hypoxia induced right ventricular wall thickening is attenuated by rapamycin Hearts of mice housed for three weeks at hypobaric hypoxia were characterized by a marked thickening of the wall of the right ventricle.

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