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J Appl Physiol 92: 2625-2632, 2002; doi:10.1152/japplphysiol.00818.2001
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Vol. 92, Issue 6, 2625-2632, June 2002

Mechanisms of aortic smooth muscle hyporeactivity after prolonged hypoxia in rats

Mary E. Zacour1, Hwee Teoh2, Andrew J. Halayko3, and Michael E. Ward2

1 Meakins-Christie Laboratories, McGill University, Montreal H3A 2T5; 2 St. Michael's Hospital, University of Toronto, Toronto M5B 5W8; and 3 Asthma/COPD Research Centre, Section of Respiratory Diseases, University of Manitoba, Winnipeg, Canada R3T 2N2

The aim of this study was to determine whether the effects of hypoxia on aortic contractility reflect a decrease in smooth muscle activation [phosphorylation of the 20-kDa myosin regulatory light chain (LC20)], the capacity for myofibrillar ATP hydrolysis (mATPase activity), or both. Our results indicate that, in endothelium-denuded aortic rings from rats exposed to hypoxia for 48 h (inspired O2 concentration = 10%), contractions to phenylephrine and potassium chloride (KCl) are impaired compared with rings from normoxic rats. The proportion of phosphorylated to total LC20 during aortic contraction induced by 10-5 M phenylephrine was reduced after hypoxia (51.4 ± 5.4% in normoxic control rats vs. 32.5 ± 4.7% in hypoxic rats, P < 0.01). Aortic mATPase activity was also decreased (maximum ATPase rate = 29.6 ± 3.4 and 20.7 ± 3.7 nmol · min-1 · mg protein-1 in control and hypoxic rats, respectively, P < 0.05). Neither proliferation nor dedifferentiation of aortic smooth muscle was evident in this model; immunostaining for smooth muscle expression of the proliferating cell nuclear antigen was negative and smooth muscle-specific isoforms of myosin heavy chains, h-caldesmon, and calponin were increased, not decreased, after hypoxic exposure. Decreased aortic reactivity after hypoxia is associated with both impairment of smooth muscle activation and diminished capacity of the actomyosin complex, once activated, to hydrolyze ATP. These changes cannot be attributed to smooth muscle dedifferentiation or to reduced contractile protein expression.

systemic circulation; vascular smooth muscle; contractile protein expression; blood flow regulation; oxygen delivery.


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