Sustained pulmonary hypertension and right ventricular hypertrophy after chronic hypoxia in mice with congenital deficiency of nitric oxide synthase 3.
作者： W Steudel , M Scherrer-Crosbie , K D Bloch , J Weimann , P L Huang
DOI: 10.1172/JCI2356
关键词:
摘要: Chronic hypoxia induces pulmonary hypertension and right ventricular (RV) hypertrophy. Nitric oxide (NO) has been proposed to modulate the vascular response hypoxia. We investigated effects of congenital deficiency endothelial NO synthase (NOS3) on responses breathing 11% oxygen for 3-6 wk. After 3 wk hypoxia, RV systolic pressure was greater in NOS3-deficient than wild-type mice (35+/-2 vs 28+/-1 mmHg, x+/-SE, P < 0.001). Pulmonary artery (PPA) incremental total resistance (RPI) were (PPA 22+/-1 19+/-1 0.05 RPI 92+/-11 55+/-5 mmHg.min.gram.ml-1, 0.05). Morphometry revealed that proportion muscularized small vessels almost fourfold mice. 6 increase free wall thickness, measured by transesophageal echocardiography, weight/body weight ratio more marked (RV thickness 0.67+/-0.05 0.48+/-0.02 mm, 0.01 2.1+/-0.2 1.6+/-0.1 mg. gram-1, hypertrophy produced chronic prevented 20 parts per million both genotypes These results suggest NOS3 enhances hypoxic remodeling hypertension, hypertrophy, production is vital counterbalance vasoconstriction caused stress.
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