ANF AND ANGIOTENSIN-II INTERACT VIA KINASES IN THE PROXIMAL STRAIGHT TUBULE

Atrial natriuretic factor (ANF) inhibits fluid absorption (J(v)) in the proximal straight tubule (PST) only after stimulation with angiotensin II (ANG II). To investigate ANF's dependency on ANG II for transport inhibition, we blocked and mimicked angiotensin's second messenger cascades and then examined ANF's ability to inhibit J(v). ANG II (10(-10) M)-stimulated J(v) was 0.47 +/- 0.10 nl . mm(-1). min(-1). After ANF (10(-10) M) was added to the bath, J(v) fell by approximate to 40% (P < 0.05). ANG II stimulates J(v) via activation of protein kinase C (PKC) and decreasing protein kinase A (PKA) activity. We inhibited PKA with H-89. In the presence of only H-89, J(v) was 0.75 +/- 0.11 nl . mm(-1). min(-1). After ANF was added to the bath J(v) fell by 30% (P < 0.05). Intracellular adenosine 3',5'-cyclic monophosphate content was not affected by ANF in the presence of ANG II. ANF could not inhibit J(v) in the presence of ANG II and 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor. KT-5823, a guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase inhibitor, blocked the action of ANF on J(v) (P > 0.30). PKC inhibition did not prevent the decrease in J(v) induced by ANF. We conclude that ANF inhibits ANG II-induced stimulation of transport by a mechanism that requires phosphorylation mediated by cGMP-dependent protein kinase subsequent to a decrease of PKA activity.