title: Salt sensitivity in blacks: evidence that the initial pressor effect of NaCl involves inhibition of vasodilatation by asymmetrical dimethylarginine.
abstract: In healthy, mostly normotensive blacks, 19 salt-sensitive (SS) and 18 salt-resistant (SR), we tested the hypothesis that, in SS subjects, dietary NaCl loading induces its initial pressor effect by inducing a normal increase of cardiac output, while failing to induce a normal pressor-offsetting vasodilatation, consequent to its inhibition by asymmetrical dimethylarginine that is abnormally increased by NaCl. In SS and SR subjects, dietary NaCl loading, 250 from 30 mmol/d, over a 7-day period, induced similar, immediate increases in external Na(+) balance (by day 2, ≈360 mmol), plasma volume (+11%), and cardiac output (+8%). In SR subjects, from day 1, transient decreases occurred in both systemic vascular resistance (nadir: -13%, day 2) and mean arterial pressure (nadir: -5%, day 2). In SS subjects, systemic vascular resistance did not change over days 1 to 3, whereas mean arterial pressure increased progressively after day 1, ultimately by 10 mm Hg. Failure of systemic vascular resistance to normally decrease, while cardiac output normally increased, accounted for salt's initial pressor effect in the SS subjects. In SS subjects, baseline plasma levels of asymmetrical dimethylarginine (0.76 μmol/L) and symmetrical dimethylarginine (0.60 μmol/L), which does not affect vasodilatation, approximated those in SR subjects. In SS but not SR subjects, NaCl loading induced increases in asymmetrical dimethylarginine on both days 2 (+38%, median) and 7 (+14%, median). Symmetrical dimethylarginine changed in neither group. For all of the subjects combined, changes in asymmetrical dimethylarginine on day 2 predicted changes in systemic vascular resistance (R=0.751; P<0.001) and mean arterial pressure (R=0.527; P=0.006) on day 2 and similarly on day 7. These observations support the hypothesis tested.
authors.affiliation: Jr, University of California San Francisco, 505 Parnassus Ave, 1291 Moffitt Hospital, San Francisco, CA 94143-0126, USA. olga@picasso.ucsf.edu
authors.forename: Olga
authors.initials: O
authors.lastname: Schmidlin
authors.forename: Alex
authors.initials: A
authors.lastname: Forman
authors.forename: Anna
authors.initials: A
authors.lastname: Leone
authors.forename: Anthony
authors.initials: A
authors.lastname: Sebastian
authors.forename: R Curtis
authors.initials: RC
authors.lastname: Morris
mesh_terms: D000328:Adult; D001741:Black or African American; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000208:ethnology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D017673:Sodium Chloride, Dietary; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine