Myosin isoform shifts and decreased reactivity in hypoxia-induced hypertensive pulmonary arterial muscle

• Published in: American journal of physiology. Lung cellular and molecular physiology 1998-05, Vol.274 (5), p.775-L785
• Main Authors: Packer, C. S, Roepke, J. E, Oberlies, N. H, Rhoades, R. A
• Format: Article
• Language: English
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.1998.274.5.L775

Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis, Indiana 46202 The principal stimulus that evokes pulmonary hypertension is chronic alveolar hypoxia. Pulmonary hypertension is associated with remodeling of the vessel walls, involving hypertrophy and hyperplasia of pulmonary arterial smooth muscle (PASM) and a concomitant increase in the deposition of connective tissue, resulting in increased wall thickness. The purpose of the present study was to determine the effect of hypoxia-induced hypertension on the structure and function of PASM. Experiments were designed to determine whether hypoxia-induced pulmonary hypertension is associated with alterations in PASM: 1 ) reactivity to a variety of agonists, 2 ) contractile protein proportions and isoforms, and 3 ) structural properties. Young adult male rats were made hypoxic by lowering the fraction of inspired O 2 (10%) for 14 days. Pulmonary arterial segments were isolated and dose-response curves to various agonists (high K + , norepinephrine, serotonin, angiotensin II, and adenosine) were generated. Gel electrophoresis was used to measure changes in the relative amounts of actin or myosin and of myosin heavy chain (MHC) isoforms. Structural changes were correlated with the pharmacological and biochemical data. Hypoxia-induced pulmonary hypertension caused a general decreased reactivity, an increase in the proportion of nonmuscle to muscle MHC isoforms in PASM, and an increase in arterial wall thickness with PASM hypertrophy or hyperplasia. myosin heavy chain isoforms; arterial smooth muscle; decreased contractility; hypertrophy; hyperplasia