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1 Physiology, Otago University, Dunedin, Otago, New Zealand; Biochemistry, National Cardiovascular Centre Research Institute, Suita, Osaka, Japan
2 Physiology, Monash University, Melbourne, Victoria, Australia
3 Biochemistry, National Cardiovascular Centre Research Institute, Suita, Osaka, Japan
4 Japan Synchrotron Radiation Research Institute, Hyogo, Japan
5 Faculty of Health Sciences, Hiroshima International University, Hiroshima, Japan
* To whom correspondence should be addressed. E-mail: jaynedaryl{at}yahoo.co.nz.
Structural and functional changes of the pulmonary circulation, particularly during the pathogenesis of pulmonary arterial hypertension (PAH), remain to be fully elucidated. In this study we utilize monochromatic synchrotron radiation (SR) microangiography for assessing changes in pulmonary arteriole blood flow in the intact-chest rat following four weeks of chronic hypoxia. Sprague-Dawley rats were exposed to normoxia (N-Rat) or chronic hypoxia (10% O2; CH-rat) for 28 days. Rats were anesthetized and microangiography was performed on the left lung to assess i) the branching distribution of pulmonary arteriole blood flow (internal diameter >80 um) and, ii) dynamic changes in vessel lumen diameter during acute hypoxic (8% O2, for 4 min) pulmonary vasoconstriction (HPV) - before and after
-adrenoceptor blockade (propranolol, 2 mg/kg, i.v.). Using SR angiography we observed that the number of opaque 3rd and 4th generation vessels (100-300 µm) for CH-rats was significantly fewer than that of N-rats. The magnitude of HPV was not different between CH-rats and N-rats.
-adrenoceptor blockade accentuated the HPV in 200-300 µm vessels for CH-rats, but even more so in N-rats. However, in CH-rats alone
-adrenoceptor blockade also accentuated the HPV in 100-200 µm vessels. In summary, we have utilized SR to assess gross blood flow changes and functional changes (i.e. HPV) of the pulmonary circulation in PAH. These results highlight the benefits of SR for assessing pulmonary circulatory pathology. Of particular importance, future use of SR will provide an effective method for assessing potential therapeutic treatments for PAH.
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