Basal lung mechanics and airway and pulmonary vascular responsiveness in different inbred mouse strains

Little is known about interstrain variations in baseline lung functions or smooth muscle contractility in murine lungs. We therefore examined basal lu ng mechanics and airway, as well as vascular reactivity to methacholine, th romboxane (using U-46619), and endothelin-1 (ET-1), A/J, AKR, BALB/c, C3H/H eN, C57BL/6, and SCID mice. All experiments were performed with isolated pe rfused mouse lungs. Except AKR, mice (which were excluded from further anal ysis), all other strains showed stable pulmonary compliance, pulmonary resi stance, and pulmonary arterial pressure within a control period of 45 min. Among these strains, C3H/HeN mice exhibited higher dynamic pulmonary compli ance and lower pulmonary resistance, whereas SCID mice had higher baseline pulmonary resistance than the other strains. Concentration-response experim ents with methacholine showed a lower airway reactivity for C57BL/6 mice co mpared with the other strains. Perfusion with 1 mu M U-46619 or 100 nM ET-1 revealed a similar pattern: the agonist-inducible broncho- and vasoconstri ction was lower in C57BL/6 mice than in all other strains, whereas it tende d to be higher in SCID mice. The present study demonstrates a correlation b etween airway and vascular responsiveness in all tested strains. SCID mice are hyperreactive, whereas C57BTJ6 mice are hyporeactive, to smooth muscle constrictors. Lung mechanics, as well as airway and vascular responsiveness , appear to be genetically controlled.