title: Impaired inactive to active kallikrein conversion in human salt-sensitive hypertension.
abstract: Active and inactive urinary kallikrein excretion rates were evaluated in 43 essential hypertensive men (45.4 +/- 5.6 yr) after normal-(120 mmol/day), low-(20 mmol/day), and high-(240 mmol/day) NaCl diets were given for 2 wk each. Patients were classified as salt-sensitive, salt-resistant, or counterregulating, on the basis of their blood pressure responses to the different NaCl intakes. Resulting data show that active and inactive kallikrein excretion rates were lower (P < 0.001) in salt-sensitive (active, 0.59 +/- 0.27 U/24 h; inactive, 3.45 +/- 1.31 U/24 h) than in salt-resistant (active, 1.41 +/- 0.35 U/24 h; inactive, 6.93 +/- 2.68 U/24 h) and in counterregulating hypertensive patients (active, 1.37 +/- 0.39 U/24 h; inactive, 6.32 +/- 2.58 U/24 h) after the normal NaCl diet. Salt-sensitive hypertensive patients showed also higher plasma digoxin-like substance (P < 0.001), atrial natriuretic peptide (P < 0.001), and fasting insulin (P < 0.005) levels than the other subgroups. Active kallikrein decreased after high and increased after low-NaCl intake in all groups. Inactive kallikrein varied similarly to active one in salt-resistant patients and counterregulating patients, whereas it increased during salt-loading in salt-sensitive patients. Consequently, the active/total kallikrein ratio decreased in salt-sensitive patients (from 20.2 +/- 3.5 to 5.82 +/- 1.02%, P < 0.05) when they switched from low- to high-NaCl intake, and the ratio was lower in these patients than in the other subgroups (P < 0.0001) after the high-NaCl diet. In conclusion, active and inactive kallikrein excretions after normal-NaCl intake are reduced in salt-sensitive hypertensive patients. The divergent active and inactive kallikrein responses to dietary NaCl changes in salt-sensitive patients could indicate an impairment of inactive to active kallikrein conversion during NaCl loading as a new mechanism in human salt-sensitive hypertension.
authors.affiliation: Department of Experimental Medicine, University of L'Aquila, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Bellini
authors.forename: C
authors.initials: C
authors.lastname: Ferri
authors.forename: A
authors.initials: A
authors.lastname: Carlomagno
authors.forename: S
authors.initials: S
authors.lastname: Necozione
authors.forename: A R
authors.initials: AR
authors.lastname: Lepore
authors.forename: G
authors.initials: G
authors.lastname: Desideri
authors.forename: A
authors.initials: A
authors.lastname: Santucci
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002985:Clinical Protocols; D018592:Cross-Over Studies; D004039:Diet, Sodium-Restricted; D004311:Double-Blind Method; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology; D017136:Ion Transport; D007610:Kallikreins / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D012964:Sodium / Q000097:blood; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D008074:Lipoproteins; D017673:Sodium Chloride, Dietary; D012964:Sodium; D007610:Kallikreins