Changes in pulmonary blood flow distribution in monocrotaline compared with hypoxia-induced models of pulmonary hypertension: assessed using synchrotron radiation.
BACKGROUND
We have previously described anatomical changes in pulmonary blood flow distribution in chronic hypoxic rats, associated with pulmonary arterial hypertension (PAH).


METHODS
In this study, we utilized synchrotron radiation microangiography to compare these changes in pulmonary blood flow with a PAH-model induced with monocrotaline (MCT), as the etiology for these two models of PAH is different. Three weeks after a subcutaneous injection of MCT (60 mg/kg) or vehicle (control), Sprague-Dawley rats were anesthetized, and microangiography was performed on the left lung to assess branching distribution of pulmonary blood flow and changes in vessel diameter during acute (8% O2 for 4 min) hypoxic pulmonary vasoconstriction--before and after sympathetic beta-adrenoceptor blockade (propranolol, 2 mg/kg, intravenous). Comparisons were made with chronic hypoxic rats using data previously published.


RESULTS
We observed that adverse changes in pulmonary blood flow were comparable for both chronic hypoxia and MCT models of PAH. Specifically, the number of opaque third and fourth generation vessels was significantly and equally fewer than that of control rats. The acute hypoxic pulmonary vasoconstriction was not altered in the hypertensive lung, though sympathetic modulation of pulmonary vasoreactivity was enhanced by chronic hypoxia, but not MCT.


CONCLUSIONS
In summary, we have demonstrated comparable adverse changes in pulmonary blood flow for chronic hypoxia and MCT models of PAH. In contrast, modulation of the hypoxic pulmonary vasoconstriction differs between the two PAH models, likely due to the impact that different pathological pathways have on the physiology of the whole organism. Such differences between models of PAH should be considered in future studies.
Department of Physiology, University of Otago, Dunedin, New Zealand. daryl.schwenke@stonebow.otago.ac.nz
Daryl O
DO
Schwenke
James T
JT
Pearson
Akito
A
Shimochi
Kenji
K
Kangawa
Hirotsugu
H
Tsuchimochi
Keiji
K
Umetani
Mikiyasu
M
Shirai
Patricia A
PA
Cragg
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000792:Angiography; D000818:Animals; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications*; D008168:Lung / Q000098:blood supply*; D008297:Male; D011433:Propranolol / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D017356:Synchrotrons
D000319:Adrenergic beta-Antagonists; D011433:Propranolol