Inhibition by epinephrine of AVP- And c AMP-stimulated Na⁺ and water transport in Dahl rat CCD

We examined the effects of epinephrine in perfused cortical collecting ducts (CCD) isolated from inbred Dahl-Rapp salt-sensitive (SS) and salt-resistant (SR) rats and from Sprague-Dawley (SD) rats. Rats were treated with 2.5 mg deoxycorticosterone pivalate (DOC; depot injection 4-9 days before study), and the CCD were treated with 220 pM vasopressin (AVP) to maximize Na⁺ transport. In CCD from all three strains 10 μM epinephrine in the bathing solution completely inhibited net Na⁺ transport, osmotic water permeability (P_f), and transepithelial voltage. In the SS CCD, epinephrine increased the fractional resistance of the luminal membrane to the same extent as 10 μM amiloride, indicating that it blocked the amiloride-sensitive conductance of the luminal membrane. Even at 100 nM epinephrine inhibited 80-100% of Na⁺ and water transport, and 1 μM yohimbine reversed or prevented these effects. In SS CCD, 0.1 mM 8-bromoadenosine 3′,5′-cyclic monophosphate (8-BrcAMP) plus 0.1 mM 3-isobutyl-1-methylxanthine in place of AVP increased lumen-to-bath Na⁺ flux (J) from 56 ± 5 to 143 ± 3 pmol·min^-1·mm^-1 and P_f from 6 ± 12 to 1067 ± 152 μm/s, but 100 nM epinephrine still significantly inhibited cAMP-stimulated J_1-b and P_f by 40 ± 5% and 31 ± 9%, respectively. Similar results were observed in the SR and SD rat CCD; however, the ability of yohimbine to reverse the epinephrine effect on cAMP-dependent transport was variable among the rat strains. We conclude that epinephrine acts via an α₂-receptor to inhibit adenylate cyclase but that at least one additional intracellular second messenger system may be involved.