Cardiotrophin-1 is a prophylactic against the development of chronic hypoxic pulmonary hypertension in rats.
BACKGROUND
Cardiotrophin-1 (CT-1) reduces arterial blood pressure by activating nitric oxide synthesis. This study attempted to elucidate the effect of CT-1 on pulmonary arteries of pulmonary hypertensive rats.


METHODS
Pulmonary hypertension was induced in rats in a hypoxic chamber containing 10% to 11% oxygen. Rats kept in the hypoxic environment received either recombinant mouse CT-1 at a concentration of 50 micro g/kg (CT-1+hypoxia group, n = 21) or phosphate-buffered saline (hypoxia group, n = 30) once per day. Control rats housed in room air also received either the equivalent concentration of CT-1 (CT-1+normoxia group, n = 18) or phosphate-buffered saline (normoxia group, n = 39). Pulmonary arterial pressure, pulmonary vasorelaxation, and ventricular hypertrophy were measured.


RESULTS
The mean pulmonary arterial pressures were as follows (from lowest to highest; p values are relative to the hypoxia group): normoxia group (20.3 +/- 4.0 mm Hg, p < 0.0001), CT-1+normoxia group (21.1 +/- 2.4 mm Hg, p < 0.0001), CT-1+hypoxia group (27.9 +/- 4.1 mm Hg, p = 0.0019), and hypoxia group (33.9 +/- 6.6 mm Hg). The endothelium-dependent vasorelaxation value was largest in the normoxia group (59.5% +/- 17.4%, p < 0.0001), with it decreasing in the other groups in the following order (p values are relative to the hypoxia group): CT-1+normoxia group (52.8% +/- 15.5%, p = 0.0005), CT-1+hypoxia group (42.3% +/- 14.8%, p = 0.0061), and hypoxia group (17.4% +/- 4.8%). Right ventricular hypertrophy was significant only in the hypoxia group.


CONCLUSIONS
Our results demonstrate that treatment with CT-1 in a chronic hypoxic pulmonary hypertension model protects the endothelial function of the pulmonary artery; decreases pulmonary arterial pressure; and attenuates right ventricular hypertrophy.
Nomura
Norikazu
N
Department of Cardiovascular Surgery, Regulatory Cell Physiology, Gastroenterological Surgery, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
Asano
Miki
M
Saito
Takayuki
T
Sasaki
Shigeru
S
Suzuki
Hikaru
H
Manabe
Tadao
T
Mishima
Akira
A
D000704:Analysis of Variance; D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000494:pharmacology*; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D000860:Hypoxia / Q000517:prevention & control*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011336:Probability; D011651:Pulmonary Artery / Q000187:drug effects; D011659:Pulmonary Gas Exchange; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014664:Vasodilation / Q000502:physiology
D016207:Cytokines; C092073:cardiotrophin 1; D019001:Nitric Oxide Synthase