Biphasic increasing effect of angiotensin-II on intracellular free calcium in isolated rat early proximal tubule.

In the freshly isolated early proximal tubule (S1), the effect of angiotensin II (ANG II) on cytosolic Ca++ concentration ([Ca++]i) was determined using the fluorescent indicator fura-2. In order to establish an adequate experimental system, we investigated firstly the relationship between cellular ATP and [Ca++]i under various conditions in late proximal tubule, the most fragile nephron segment, and cortical collecting tubule, a relatively stable one. We found out that cellular ATP depletion caused [Ca++]i to rise, and ANG II response to [Ca++]i under high ATP condition was higher than that under low ATP condition. ANG II-induced [Ca++]i rise in S1 was biphasic, demonstrating the two peaks corresponding to the 10(-11) and 10(-7) M ANG II. This study suggests for the first time 1) the necessity of high intracellular ATP to evaluate a high affinity ANG II actions and 2) the biphasic characteristics of [Ca++]i increase by ANG II in intact S1.