AJP - Renal Physiology, Vol 250, Issue 5 759-F769, Copyright © 1986 by American Physiological Society

ARTICLES

Angiotensin-receptor signaling in cultured vascular smooth muscle cells

J. B. Smith

Functional receptors for angiotensin II (ANG II) are present in smooth muscle cells cultured from rat aorta. These cells are especially suitable for investigating transmembrane signaling events, since ANG II-receptor function is consistently expressed for many population doublings in culture. Cytoplasmic free Ca, measured with quin 2 or fura-2, transiently increases after receptor stimulation. ANG II releases Ca that is sequestered intracellularly, since the removal of extracellular Ca does not prevent the hormone from increasing intracellular free Ca. Angiotensin provokes both polyphosphoinositide hydrolysis and phosphatidate-phosphoinositide synthesis. Purified inositol trisphosphate (IP3) releases Ca from a nonmitochondrial organelle, presumably the sarcoplasmic reticulum or a specialized region therein. IP3 probably opens an intracellular Ca channel by a ligand-binding reaction rather than a metabolic reaction. The accumulation of IP3 in intact cells in response to ANG II seems fast enough to cause Ca mobilization. ANG II increases a fast and a slow component of 45Ca2+ efflux from the intact cells. The rapid stimulation of Ca2+ efflux from the cell via a Na-Ca antiporter probably accounts at least in part for the short duration of the increase in cytoplasmic free Ca elicited by angiotensin. ANG II has no effect on a fast component of 45Ca2+ influx but does increase a slow component of 45Ca2+ influx; that increase would help to sustain the elevation in free Ca and the refilling of the sarcoplasmic reticulum. Additionally, ANG II-receptor stimulation depolarizes the cell membrane and increases the specific activities of the Na-K pump, the Na-H antiporter, the Na-Ca antiporter, and the Na-K-Cl cotransporter. Ca and/or 1,2-diacylglycerol, the lipophilic activator of protein kinase C, which is concomitantly produced along with IP3, may mediate the effects of ANG II on Na and K transport. Investigations of cultured vascular smooth muscle support the inositol-signaling hypothesis of hormone action.

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