Renal effects of angiotensin II: Modulation by calcium and cyclooxygenase products

Modulation of angiotensin II effects on renal function by extracellular calcium levels and cyclooxygenase products was evaluated using the isolated perfused rat kidney. Kidneys from normal male Sprague-Dawley rats were perfused at constant pressure. After base-line assessment of function, angiotensin II was administered as a bolus and constant infusion; group 1 with normal ionized calcium and 1.2 ng/min angiotensin II, group 2 with normal ionized calcium and 0.6 ng/min angiotensin II, group 3 with low ionized calcium and 1.2 ng/min angiotensin II, and group 4 with indomethacin, low ionized calcium, and 1.2 ng/min angiotensin II. Angiotensin II caused a marked fall in inulin clearance (C(In)) in groups 1 and 2. With low ionized calcium (group 3), angiotensin II increased resistance to the same degree as in group 2, but in contrast to group 2, C(In) was unchanged. Kidneys perfused with indomethacin (group 4) had marked angiotensin II-induced declines in C(In) that rapidly returned to base line despite persistently elevated resistance. Thus the results demonstrated that both calcium and cyclooxygenase products may directly modulate the effects of angiotensin II on renal function. These effects involve more than modulation of angiotensin II-induced vasoconstriction.