Effect of angiotensin II on calcium reabsorption by the luminal membranes of the nephron

Abstract

In the rat and the rabbit, a number of studies have reported the effects of angiotensin II (ANG II) on Na+ reabsorption by the proximal (PT) and distal (DT) convoluted tubules of the kidney. The aim of the present study was to examine the effect of ANG II on Ca2+ uptake by the luminal membranes of the PT and DT of the rabbit. Incubation of PT and DT with 10−12 M ANG II enhanced the initial Ca2+uptake in the two segments. Dose-response experiments revealed, for Ca2+ as well as for Na+ transport, a biphasic action with a maximal effect at 10−12 M. Ca2+transport by the DT luminal membrane presents a dual kinetic. ANG II action influenced the high-affinity Ca2+ channel, increasing maximal velocity from 0.72 ± 0.03 to 0.90 ± 0.05 pmol · μg−1 · 10 s−1( P < 0.05, n = 3) and leaving the Michaelis-Menten constant unchanged. The effect of ANG II was abolished by losartan, suggesting that the hormone is acting through AT1 receptors. In the PT, calphostin C inhibited the effect of the hormone. It is therefore probable that protein kinase C is involved as a messenger. In the DT, however, neither Rp cAMP, calphostin C, nor econazole (a phospholipase A inhibitor) influenced the hormone action. Therefore, the mechanisms involved in the hormone action remain undetermined. Finally, we questioned whether ANG II acts in the same DT segment as does parathyroid hormone on Ca2+transport. The two hormones increased Ca2+ transport, but their actions were not additive, suggesting that they both influence the same channels in the same segment of the distal nephron, i.e., the segment responsible for the high-affinity calcium channel.