title: Erythrocyte sodium-lithium countertransport in non-modulating offspring and essential hypertensive individuals: response to enalapril.
abstract: Non-modulators are a subset of essential hypertensive individuals in whom renal hemodynamic and adrenal aldosterone responses to angiotensin II fail to modulate appropriately during high dietary salt intake. The main aim of this study was to investigate the familial aggregation of non-modulation and several erythrocyte Na+ transport systems in normotensive and hypertensive individuals as well as offspring of hypertensive parents. An additional aim was to evaluate the effect of treatment with enalapril on erythrocyte Na+ transport. We studied 15 normotensive subjects (6 males, 27+/-6 years), 14 untreated modulating essential hypertensive subjects (7 males, 38+/-7 years), 12 untreated non-modulating essential hypertensive subjects (7 males, 38+/-6 years), 14 modulating offspring of hypertensive parents (8 males, 25+/-6 years), and 14 non-modulating offspring of hypertensive parents (8 males, 26+/-4 years). Blood pressure was recorded with an oscillometric device and renal plasma flow and glomerular filtration rate by clearances of para-aminohippurate and inulin, respectively. Non-modulating subjects were identified as individuals who failed to increase effective renal plasma flow by 30% and decrease filtration fraction by at least 30% 10 days after changing from a low (20 mmol/d) to a high (250 mmol/d) sodium intake. Erythrocyte Na+ transport was characterized by measurements of the Na+-K+ pump, Na+-Li+ countertransport, Na+-K+-Cl- cotransport, passive Na+ permeability, and Na+ content. After the initial studies, hypertensive individuals were treated with enalapril (20 mg/d P.O.) for 6 months, after which erythrocyte Na+ transport measurements were again made. The main findings were that Na+-Li+ countertransport is increased in non-modulating hypertensive subjects and non-modulating offspring of hypertensive parents, that the increase in blood pressure in response to high salt intake is greater in non-modulating than modulating hypertensive subjects, and that enalapril decreases Na+-Li+ countertransport activity to normal in non-modulating hypertensive subjects. These findings provide support for a possible genetic role in the development of salt sensitivity and suggest that Na+-Li+ countertransport and non-modulation are related phenotypes.
authors.affiliation: Hospital Instituto de Cardiología, Academia Nacional de Medicina, IICB, Fundación Universitaria Dr Rene G Favaloro, and ICYCC-Fundación Favaloro, Buenos Aires, Argentina.
authors.forename: R A
authors.initials: RA
authors.lastname: Sánchez
authors.forename: M I
authors.initials: MI
authors.lastname: Giménez
authors.forename: M
authors.initials: M
authors.lastname: Migliorini
authors.forename: C
authors.initials: C
authors.lastname: Giannone
authors.forename: A J
authors.initials: AJ
authors.lastname: Ramírez
authors.forename: A B
authors.initials: AB
authors.lastname: Weder
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001692:Biological Transport; D002712:Chlorides / Q000378:metabolism; D003627:Data Interpretation, Statistical; D004656:Enalapril / Q000008:administration & dosage / Q000627:therapeutic use*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008094:Lithium / Q000032:analysis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012964:Sodium / Q000032:analysis / Q000097:blood* / Q000378:metabolism; D012982:Sodium, Dietary / Q000009:adverse effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013054:Spectrophotometry, Atomic; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002712:Chlorides; D012982:Sodium, Dietary; D004656:Enalapril; D008094:Lithium; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase