Integrative Physiology |
From the Smooth Muscle Research Group, Department of Pharmacology and Therapeutics, University of Calgary, Alberta, Canada.
Correspondence to Rodger D. Loutzenhiser, PhD, Department of Pharmacology and Therapeutics, The University of Calgary, Health Sciences Centre, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada. E-mail rloutzen{at}ucalgary.ca
AbstractAngiotensin II (Ang II)induced Ca2+ signaling was studied in isolated rat renal arterioles using fura-2. Ang II (10 nmol/L) caused a sustained elevation in [Ca2+]i, which was dependent on [Ca2+]o in both vessel types. This response was blocked by nifedipine in only the afferent arteriole. Using the Mn2+ quench technique, we found that Ang II stimulates Ca2+ influx in both vessels. Nifedipine blocked the Ang IIinduced Ca2+ influx in afferent arterioles but not in efferent arterioles. In contrast to Ang II, KCl-induced depolarization stimulated Ca2+ influx in only the afferent arteriole. Cyclopiazonic acid (CPA, 30 µmol/L) was used to examine the presence of store-operated Ca2+ entry in myocytes isolated from each arteriole. In efferent myocytes, CPA induced a sustained Ca2+ increase that was dependent on [Ca2+]o and insensitive to nifedipine. This mechanism was absent in afferent myocytes. SKF 96365 inhibited Ang IIinduced Ca2+ entry in efferent arterioles and CPA-induced Ca2+ entry in efferent myocytes over identical concentrations. Our findings thus indicate that Ang II activates differing Ca2+ influx mechanisms in pre- and postglomerular arterioles. In the afferent arteriole, Ang II activates dihydropyridine-sensitive L-type Ca2+ channels, presumably by membrane depolarization. In the efferent arteriole, Ang II appears to stimulate Ca2+ entry via store-operated Ca2+ influx.
Key Words: renal microcirculation renal hemodynamics nifedipine cyclopiazonic acid SKF 96365
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