Endothelial ET(B) limits vascular remodelling and development of pulmonary hypertension during hypoxia.
BACKGROUND
We hypothesised that the potential protective effects of endothelial ET(B) are important in limiting pulmonary vascular muscularisation, vasoconstriction and the development of pulmonary arterial hypertension in response to hypoxia.


METHODS
EC-specific ET(B) knockout mice (EC ET(B)(-/-)) and control mice (ET(B)(f/f)) were subjected to hypobaric hypoxic (10% FiO2) or normoxic conditions for 14 days before assessment of right ventricular pressure and pulmonary vascular morphology and function.


RESULTS
During normoxia, no difference in right ventricular pressure was detected between EC ET(B)(-/-) (23.7 +/- 1.7 mm Hg) and ET(B)(f/f) mice (20.2 +/- 1.5 mm Hg). Hypoxia induced an exaggerated increase in right ventricular pressure in EC ET(B)(-/-) mice (34.4 +/- 1.2 mm Hg vs. 24.6 +/- 1.4 mm Hg), accompanied by an increase in right ventricular mass. No effect was observed in ET(B)(f/f) mice. Endothelin-1 constricted pulmonary arteries from both groups, although maximum response was similar irrespective of inspired oxygen or genotype. Hypoxia increased the percentage of muscularised vessels in both groups of mice, but the percentage increase was significantly greater in EC ET(B)(-/-) mice.


CONCLUSIONS
The potential protective effects of endothelial ET(B) are important in limiting pulmonary vascular muscularisation and the development of pulmonary arterial hypertension in response to hypoxia.
Kelland
N F
NF
Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Bagnall
A J
AJ
Morecroft
I
I
Gulliver-Sloan
F H
FH
Dempsie
Y
Y
Nilsen
M
M
Yanagisawa
M
M
Maclean
M R
MR
Kotelevtsev
Y V
YV
Webb
D J
DJ
D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D000860:Hypoxia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000503:physiopathology; D011651:Pulmonary Artery / Q000378:metabolism* / Q000503:physiopathology; D044023:Receptor, Endothelin B / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014661:Vasoconstriction; D017725:Ventricular Pressure
D019332:Endothelin-1; D044023:Receptor, Endothelin B