Effect of angiotensin II on Ca2+ kinetics and contraction in cultured rat glomerular mesangial cells.
This in vitro study was undertaken to determine the changes in Ca2+ kinetics and cell shape of cultured putative glomerular mesangial cells in the rat in response to angiotensin II (ANG II). Intracellular Ca2+ ([Ca2+]i) was measured using quin 2. ANG II-stimulated Ca2+ efflux was also determined. ANG II induced rapid concentration-dependent increases in [Ca2+]i and Ca2+ efflux. ANG II also induced contraction of mesangial cells as assessed by alterations in cell shape. Even in Ca2+-free medium, ANG II increased [Ca2+]i and Ca2+ efflux, but to a lesser extent. Under this condition, contraction of mesangial cells induced by ANG II was also observed. Readdition of extracellular Ca2+ after the ANG II-induced increase in [Ca2+]i caused a second and slower [Ca2+]i increase. High potassium (50 mM) induced a change of [Ca2+]i, but to a lesser extent compared with the ANG II-induced change. The Ca2+ channel blocker verapamil (5 x 10(-5) M) partially inhibited ANG II-induced Ca2+ influx but totally blocked the increase in [Ca2+]i induced by high potassium. Verapamil did not inhibit ANG II-stimulated Ca2+ efflux or the change in cell shape. Dantrolene (10(-4) M), a blocker of Ca2+ release from endoplasmic reticulum, inhibited ANG II-stimulated Ca2+ efflux and change in cell shape. These results indicate that ANG II rapidly increases [Ca2+]i in cultured rat mesangial cells, in part by mobilizing Ca2+ from dantrolene-sensitive intracellular pools and in part through activation of receptor-operated and voltage-dependent Ca2+ channels. The [Ca2+]i mobilization, however, seems to be the primary modulator of initial glomerular mesangial cell contraction.
Takeda
K
K
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Meyer-Lehnert
H
H
Kim
J K
JK
Schrier
R W
RW
D000634:Aminoquinolines; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003620:Dantrolene / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains; D012504:Saralasin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000634:Aminoquinolines; D000804:Angiotensin II; D014700:Verapamil; D003620:Dantrolene; D012504:Saralasin; C035739:Quin2; D002118:Calcium