Deletion of the eNOS gene has a greater impact on the pulmonary circulation of male than female mice

Miller, A. A. , Hislop, A. A., Vallance, P. J. and Haworth, S. G. (2005) Deletion of the eNOS gene has a greater impact on the pulmonary circulation of male than female mice. American Journal of Physiology: Lung Cellular and Molecular Physiology, 289(2), L299-L366. (doi: 10.1152/ajplung.00022.2005) (PMID:15821017)

Abstract

Nitric oxide is involved in development and postnatal adaptation of the pulmonary circulation. This study aimed to determine whether genetic deletion of nitric oxide synthase (NOS) would lead to maldevelopment of the pulmonary arteries in fetal life, compromise adaptation to extrauterine life, and be associated with a pulmonary hypertensive phenotype in adult life and if any abnormalities were detected, were they sex dependent. Morphometric analyses were made on lung tissue from male and female fetal, newborn, 14-day-old, and adult endothelial NOS-deficient (eNOS−/−) or inducible NOS-deficient (iNOS−/−) and wild-type mice. Hemodynamic studies were carried out on adult mice with deletion of either eNOS or iNOS genes. We found that in eNOS−/− mice, lung development was normal in fetal, newborn, and adult lungs. Pulmonary arterial muscularity was greater than normal in both male and female eNOS−/− during fetal life and at birth, but the abnormality persisted only in male mice. Right ventricular hypertrophy was present in 14-day-old and adult male eNOS−/− but not in female mice. Adult male eNOS−/− mice had higher mean right ventricular and systemic pressures than female eNOS−/− mice (P lt; 0.05). Thus deletion of the eNOS gene was associated with structural evidence of pulmonary hypertension in both sexes during fetal life, but pulmonary hypertension persisted only in the male. In neither sex did iNOS or neuronal NOS appear to compensate for the eNOS deletion. Adult iNOS−/− mice did not have structural or hemodynamic evidence of pulmonary hypertension. Possible compensatory mechanisms are discussed.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Miller, Dr Alyson
• Authors: Miller, A. A., Hislop, A. A., Vallance, P. J., and Haworth, S. G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: American Journal of Physiology: Lung Cellular and Molecular Physiology
• Publisher: American Physiological Society
• ISSN: 1040-0605
• ISSN (Online): 1522-1504