HYPERTENSIVE GLOMERULAR DAMAGE AS REVEALED BY THE EXPRESSION OF ALPHA-SMOOTH MUSCLE ACTIN AND NONMUSCLE MYOSIN

The aim of this study was to determine the phenotypic modulation in me sangial cells of glomeruli damaged by hypertension. Salt-loaded stroke -prone spontaneously hypertensive rats were untreated or treated with a calcium antagonist, manidipine (2 mg/kg/day) for eight weeks. In nor motensive Wistar-Kyoto rats, alpha-smooth muscle actin was not express ed in any glomerular cells and a non-muscle myosin heavy chain isoform , SMemb, was slightly expressed in glomerular Visceral epithelial cell s. In the untreated hypertensive rats, the glomeruli showed sclerosis to various degrees and expressed alpha-smooth muscle actin and SMemb. Normal expression of SMemb in the epithelial cells disappeared. Notabl y, alpha-smooth muscle actin-positive fibroblast-like cells appeared i n the interstitium, especially around the Bowman's capsules. Manidipin e ameliorated the glomerulosclerosis and reduced the expression of alp ha-smooth muscle actin in mesangial cells. In conclusion, the mesangia l cells changed their phenotypes and expressed alpha-smooth muscle act in and SMemb in the glomeruli during the development of hypertensive r enal damage. These phenotypically changed mesangial cells are consider ed to be activated and to produce various kinds of cytokines and extra cellular matrix, which leads to glomerulosclerosis. Manidipine attenua ted the glomerular damage and the phenotypic changes. The functional r elevance of phenotypic changes in these cells should be elucidated in future studies.