INHIBITION BY EPINEPHRINE OF AVP-STIMULATED AND CAMP-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 muM 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 muM 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 muM 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(l-->b) from 56 +/- 5 to 143 +/- 3 pmol.min-1.mm-1 and P(f) from 6 +/- 12 to 1067 +/- 152 mum/s, but 100 nM epinephrine still significantly inhibited cAMP-stimulated J(l-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 alpha2-receptor to inhibit adenylate cyclase but that at least one additional intracellular second messenger system may be involved.