Contractile properties during development of hypertrophy of the smooth muscle in the rat portal vein

Abstract

Structural and mechanical alterations during hypertrophy of the rat portal vein were investigated. Growth of the vessel was induced by a partial ligature of the vessel causing an increased transmural pressure. Vessel segments from animals kept with ligature for 1, 3, 5 and 7 days, were compared with vessels from sham-operated animals. Maximal active force and vessel cross-sectional area increased with time in the ligated group. On day 7, force and cross-sectional area at the optimal length, were markedly increased in the ligated group (21.1 +/- 1.0 mN, 0.55 +/- 0.04 mm2, n = 9) compared with the control vessels (11.7 +/- 1.0 mN, 0.30 +/- 0.02 mm2, n = 7). Light and electron microscopy of preparations fixed at optimal length showed that the amount of smooth muscle and the cross-sectional area of cell profiles were almost doubled in the ligated group on day 7, consistent with hypertrophy of the smooth muscle. The force per smooth muscle cell area was similar in the two groups (ligated: 132 +/- 15; control: 145 +/- 16 mN mm-2, n = 4-5). The maximal shortening velocity was significantly lower in the hypertrophied group (ligated: 0.28 +/- 0.02; control: 0.41 +/- 0.01 optimal length s-1, n = 6). In chemically skinned preparations, activated by maximal thiophosphorylation of the myosin light chains, force was higher in the ligated group compared to the controls but no difference in maximal shortening velocity was observed. In conclusion, the increased transmural pressure is associated with a rapid increase in the amount of smooth muscle in the portal vein. The mechanical data show that after 7 days the force generating ability of the contractile system has increased in proportion to the smooth muscle cell mass. The unaltered maximal shortening velocity in the skinned hypertrophied preparations suggests that the kinetic properties of the maximally activated contractile system are unaltered. The decreased maximal shortening velocity in the intact hypertrophied preparations may reflect alterations in the excitation-contraction coupling.

Actin Cytoskeleton Dynamics Promotes Leptin-Induced Vascular Smooth Muscle Hypertrophy via RhoA/ROCK- and Phosphatidylinositol 3-Kinase/Protein Kinase B-Dependent Pathways

“…Previously, we have studied the effect of stretch on cultured RPVs, which causes increases in contractility, protein synthesis, and cell cross-sectional area relative to unstretched, control veins (Zeidan et al, 2000). These data resemble the pattern seen with elevated venous pressure in vivo over a similar time (Malmqvist and Arner, 1988), suggesting that chronic exposure to leptin, especially under elevated conditions, may alter the structure and function of VSMC in vivo.…”

Stretch-induced contractile differentiation of vascular smooth muscle: sensitivity to actin polymerization inhibitors

“…To examine whether hypertrophic growth under in vivo conditions affects SM22 concentration, portal veins were analyzed after experimental portal hypertension (16). In 7 days, this treatment approximately doubles the amount of smooth muscle in the vessel wall, with a corresponding increase in force generation (21). Tissue concentrations of myosin and actin are essentially unaltered after hypertrophy, and thus the total amounts of these contractile proteins increase during hypertrophy in proportion to tissue mass (22).…”

“…One vessel that has been extensively investigated is the rat portal vein, in which elevated intraluminal pressure in vivo over a few days causes hypertrophy and increased contractility (16,21). In vitro, portal venous strips kept in organ culture under an applied load developed increased contractility, protein synthesis, and cell cross-sectional area compared with unloaded control strips (40).…”

Stretch-Dependent Modulation of Contractility and Growth in Smooth Muscle of Rat Portal Vein

“…Partial ligation of the rat portal vein close to its entrance into the liver hilus causes increased pressure and, within 5 to 7 days, increased contractility and marked hypertrophy of the smooth muscle layer, with increased contractile and cytoskeletal protein contents. 2,3 For elucidating mechanisms behind vascular adaptation and growth, in vitro culture offers an advantage in terms of experimental control, but it has proven difficult to maintain isolated smooth muscle cells in the contractile phenotype characteristic of the medial layer of the adult vessel wall. Cyclic stretch of smooth muscle cells grown on elastic media increases the proliferation rate as well as protein synthesis.…”