(Hypertension. 1995;26:905-911.)
© 1995 American Heart Association, Inc.
Articles |
From Instituto Reina Sofía de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca (A.R.-B., C.M.-S., A.M.R.-L., J.M.L.-N.) and Servicio de Endocrinología, Hospital Ramón y Cajal, Madrid (M.R., J.S.), Spain.
Correspondence to Dr José M. López-Novoa, Departamento de Fisiología y Farmacología, Edificio Departamental, Universidad de Salamanca, Avda. Campo Charro s/n, 37007 Salamanca, Spain.
Abstract We examined the effect of a sodium pump inhibitor isolated from bovine hypothalamus and pituitary tissues on contraction, proliferation, and calcium mobilization in primary cultures of rat mesangial cells. Hypothalamic-hypophysary inhibitory factor (HHIF) inhibited rubidium uptake in a concentration-dependent manner (0.2 U/mL: 56.8±6.3% inhibition). It also induced a concentration- and time-dependent decrease in planar cell surface area. Maximal contraction (25±5% reduction in cell size) was reached at 60 minutes with a concentration of 0.2 U/mL. This effect was inhibited by both verapamil and TMB-8 (10-5 mol/L). HHIF was also observed to increase DNA synthesis (0.2 U/mL: 4361±168 versus 2129±162 cpm per well under control conditions) and cell proliferation (0.2 U/mL: 52 290±1931 versus 10 512±121 cells per well under control conditions). Both effects were also inhibited by verapamil and TMB-8. Moreover, HHIF induced the expression of immediate early genes c-fos and c-jun mRNA. HHIF-induced effects were accompanied by an increase in cytosolic free calcium (203±58 versus 101±2 nmol/L under control conditions), which was inhibited by verapamil and TMB-8. In summary, HHIF induces mesangial cell contraction and proliferation; these effects seem to be mediated by an increase in cytosolic free calcium levels.
Key Words: mesangium, glomerular hypertension, essential Na+,K+-transporting ATPase genes
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