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 sa lt-resistant (SR) rats and from Sprague-Dawley (SD) rats. Rats were tr eated with 2.5 mg deoxycorticosterone pivalate (DOC; depot injection 4 -9 days before study), and the CCD were treated with 220 pM vasopressi n (AVP) to maximize Na+ transport. In CCD from all three strains 10 mu M epinephrine in the bathing solution completely inhibited net Na+ tra nsport, osmotic water permeability (P(f)), and transepithelial voltage . In the SS CCD, epinephrine increased the fractional resistance of th e luminal membrane to the same extent as 10 muM amiloride, indicating that it blocked the amiloride-sensitive conductance of the luminal mem brane. Even at 100 nM epinephrine inhibited 80-100% of Na+ and water t ransport, 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 lume n-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 th e 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 intracel lular second messenger system may be involved.