Angiotensin II-induced Ca(2+) influx in renal afferent and efferent arterioles: differing roles of voltage-gated and store-operated Ca(2+) entry.
Angiotensin II (Ang II)-induced Ca(2+) signaling was studied in isolated rat renal arterioles using fura-2. Ang II (10 nmol/L) caused a sustained elevation in [Ca(2+)](i), which was dependent on [Ca(2+)](o) in both vessel types. This response was blocked by nifedipine in only the afferent arteriole. Using the Mn(2+) quench technique, we found that Ang II stimulates Ca(2+) influx in both vessels. Nifedipine blocked the Ang II-induced Ca(2+) influx in afferent arterioles but not in efferent arterioles. In contrast to Ang II, KCl-induced depolarization stimulated Ca(2+) influx in only the afferent arteriole. Cyclopiazonic acid (CPA, 30 micromol/L) was used to examine the presence of store-operated Ca(2+) entry in myocytes isolated from each arteriole. In efferent myocytes, CPA induced a sustained Ca(2+) increase that was dependent on [Ca(2+)](o) and insensitive to nifedipine. This mechanism was absent in afferent myocytes. SKF 96365 inhibited Ang II-induced Ca(2+) entry in efferent arterioles and CPA-induced Ca(2+) entry in efferent myocytes over identical concentrations. Our findings thus indicate that Ang II activates differing Ca(2+) influx mechanisms in pre- and postglomerular arterioles. In the afferent arteriole, Ang II activates dihydropyridine-sensitive L-type Ca(2+) channels, presumably by membrane depolarization. In the efferent arteriole, Ang II appears to stimulate Ca(2+) entry via store-operated Ca(2+) influx.
Loutzenhiser
K
K
Smooth Muscle Research Group, Department of Pharmacology and Therapeutics, University of Calgary, Alberta, Canada.
Loutzenhiser
R
R
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001160:Arterioles / Q000378:metabolism; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D016257:Fura-2 / Q000378:metabolism; D006439:Hemodynamics; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008345:Manganese / Q000378:metabolism; D008833:Microcirculation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000804:Angiotensin II; D008345:Manganese; D002118:Calcium; D016257:Fura-2