ANF inhibits norepinephrine-stimulated fluid absorption in rat proximal straight tubules.

We have previously shown that atrial natriuretic factor (ANF) only inhibits fluid absorption in the proximal straight tubule after the tissue has been exposed to angiotensin (ANG) II. In this paper, the interaction between ANF and norepinephrine (NE) in the proximal straight tubule was investigated. ANF alone (10(-9) M) added to the bath had no significant effect on fluid absorption. In contrast, when tubules were first treated with 10(-7) M NE, 10(-9) M ANF reduced fluid absorption from 0.63 +/- 0.09 to 0.41 +/- 0.04 nl.mm-1.min-1. NE alone stimulated fluid absorption by 33%. Dibutyryl-guanosine 3',5'-cyclic monophosphate (cGMP; 50 microM) mimicked the effects of ANF, reducing fluid absorption from 0.73 +/- 0.06 to 0.35 +/- 0.07 nl.mm-1.min-1 in NE-treated tubules. However, it had no effect on fluid absorption in the absence of NE. These studies suggest that 1) ANF can regulate fluid absorption in the proximal nephron; 2) this inhibition occurs only after transport has been stimulated by agents such as NE (or ANG II); 3) cGMP is part of the second messenger system of ANF in the rat proximal straight tubule; and 4) the primary interaction between ANF and NE (or ANG II) occurs in the second messenger cascades subsequent to steps that affect levels of cGMP.