Mechanism of action of angiotensin II on isolated rat glomeruli.
Angiotensin II (Ang II) regulates glomerular filtration rate by contracting mesangial cells and thereby decreasing glomerular filtration surface area. To elucidate the cellular mechanism of this action, we investigated the roles of Ca and protein kinase C (PKC) activation in Ang II-induced glomerular capillary vasoconstriction using 3H-inulin to measure the extracellular (largely intracapillary) volume of isolated decapsulated rat glomeruli. Ang II (1 microM) rapidly decreased the glomerular inulin space (GIS), bringing about a maximal decrease at five minutes, which lasted up to 30 minutes. When incubated in 0.5 mM EGTA-containing Ca-free medium or in the presence of 1 microM diltiazem or verapamil, the sustained phase (after 7 min) was completely inhibited. The initial effect (at 3 and 5 min) was only partially inhibited by these maneuvers but was completely inhibited by trifluoperazine or W-7, which indicated that it was dependent on calmodulin and, accordingly, on Ca probably released from the intracellular store. The sustained effect was mimicked by 12-0-tetradecanoylphorbol-13-acetate (TPA) in the presence of extracellular Ca, but was not in its absence. The sustained effect was also inhibited by H-7, an inhibitor of PKC, and by W-7, which indicated that PKC activation and influx of extracellular Ca are both important. Combined treatment with A23187 and TPA could mimic both the initial and sustained effect of Ang II in the presence of extracellular Ca, though either one of them failed to do so when used alone. These results suggest that the initial effect of Ang II on GIS is mediated by Ca released from the intracellular store, on the one hand, and the sustained effect by extracellular Ca influx and PKC activation, on the other.
Fujiwara
Y
Y
First Department of Medicine, Osaka University Medical School, Japan.
Kitamura
E
E
Ueda
N
N
Fukunaga
M
M
Orita
Y
Y
Kamada
T
T
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D005919:Glomerular Filtration Rate; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D000804:Angiotensin II; D011493:Protein Kinase C; D002118:Calcium