title: Regulation of glomerular filtration in essential hypertension: role of abnormal Na+ transport and atrial natriuretic peptide.
abstract: BACKGROUND
  Many studies conducted in the last two decades have aroused interest in the role of glomerular hyperfiltration in the pathogenesis of renal damage in hypertension. Glomerular hyperfiltration has been mainly attributed to intraglomerular hypertension and overactivity of the renin-angiotensin system, but not much is known about the role of excessive renal proximal tubule Na+ reabsorption, which may activate tubuloglomerular feedback and increase glomerular filtration. Therefore, we evaluated the relationships between glomerular hemodynamics, plasma atrial natriuretic peptide (ANP) concentration, proximal tubule Na+ reabsorption, assessed by renal Li+ reabsorption, and sodium-lithium exchange (NLE) in circulating erythrocytes ex vivo, a marker of increased protein expression of isoform 3 of the sodium-proton exchanger (NHE-3) in the proximal tubule, in essential hypertensive patients.
  
  
  METHODS
  32 patients with essential hypertension were investigated after a two week placebo wash out period and after four-weeks treatment with open-label angiotensin converting enzyme inhibitors (ACEI). Before and after active treatment the following parameters were assessed: blood pressure (mercury sphygmomanometry), glomerular filtration rate (GFR), renal plasma flow, and lithium clearance (clearances of inulin, PAH and orally administered lithium, respectively), plasma ANP (radioimmunoassay), and, only at baseline, plasma renin activity, plasma and urinary aldosterone (radioimmunoassay) and NLE (sodium stimulated lithium efflux).
  
  
  RESULTS
  Baseline GFR was positively correlated with NLE, Li+ clearance and ANP, and the patients with elevated NLE (> or =0.4 mmol/L cell/h) (31%) had higher GFR and ANP than the patients with normal NLE, but similar plasma renin activity, plasma and urinary aldosterone. ACEI reduced GFR and its change was negatively correlated with pretreatment GFR and NLE and positively with the change of proximal tubule Na+ reabsorption. After ACEI, ANP increased in patients with normal NLE but not in those with high NLE (p<0.001 for the difference).
  
  
  CONCLUSIONS
  Increased proximal tubule Na+ reabsorption contributes to the pathophysiology of glomerular hyperfiltration in patients with essential hypertension, and is compensated by increased ANP levels. It can be corrected by short-term ACEI treatment.
authors.affiliation: Department of Clinical and Experimental Medicine, 4th Clinical Medicine, University of Padova, Italy. andrea.semplicini@unipd.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Semplicini
authors.forename: Giulio
authors.initials: G
authors.lastname: Ceolotto
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Sartori
authors.forename: Andrea
authors.initials: A
authors.lastname: Maresca
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Baritono
authors.forename: Renzo
authors.initials: R
authors.lastname: De Toni
authors.forename: Italia
authors.initials: I
authors.lastname: Paparella
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Calò
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D009320:Atrial Natriuretic Factor / Q000032:analysis / Q000378:metabolism*; D001795:Blood Pressure Determination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values; D017595:Renal Plasma Flow / Q000187:drug effects; D012084:Renin-Angiotensin System; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D009320:Atrial Natriuretic Factor