title: Sodium-lithium countertransport has low affinity for sodium in hyperinsulinemic hypertensive subjects.
abstract: We recently reported that incubation of red blood cells with insulin markedly decreases the affinity for external Na+ and increases the maximal transport rate (Vmax) of Na(+)-Li+ countertransport. The association of hypertension with insulin resistance and its compensatory hyperinsulinemia led us to investigate the relationship between insulin levels in vivo and the Na+ activation kinetics of this antiporter. We studied normotensive (n = 28) and hypertensive (n = 25) subjects after they had fasted overnight and determined their plasma glucose and insulin concentrations. Insulin levels were higher in the hypertensive subjects (11.7 +/- 1.5 microU/mL, mean +/- SEM) than in the normotensive subjects (8.2 +/- 1.2 microU/mL), but glucose levels were similar and within normal limits. Antiporter activity was measured as sodium-stimulated Li+ efflux by a new procedure that uses isosmotic conditions to raise external Na+ to 280 mmol/L. In normotensive subjects, Vmax was reached between 50 and 100 mmol/L Na+, whereas in most hypertensive subjects, Na+ concentrations higher than 150 mmol/L were needed. This different kinetic behavior was because the Na+ concentration for half-maximal activation (Km) was twofold higher in hypertensive subjects (58.9 +/- 5.3 mmol/L) than in normotensive subjects (29.8 +/- 2.6 mmol/L, P < .001). Hypertensive subjects with fasting insulin levels greater than 10 microU/mL (n = 12) had a higher Km for Na+ than subjects with insulin levels less than 10 microU/mL (n = 13) (73.4 +/- 8.7 versus 45.6 +/- 3.9 mmol/L, respectively, P < .01) and similar Vmax (0.57 +/- 0.05 versus 0.41 +/- 0.05 mmol.L-1.h-1).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Endocrine Hypertension Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: G
authors.initials: G
authors.lastname: Zerbini
authors.forename: G
authors.initials: G
authors.lastname: Ceolotto
authors.forename: C
authors.initials: C
authors.lastname: Gaboury
authors.forename: L
authors.initials: L
authors.lastname: Mos
authors.forename: A C
authors.initials: AC
authors.lastname: Pessina
authors.forename: M
authors.initials: M
authors.lastname: Canessa
authors.forename: A
authors.initials: A
authors.lastname: Semplicini
mesh_terms: D000328:Adult; D017920:Antiporters / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007328:Insulin / Q000097:blood*; D008094:Lithium / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012964:Sodium / Q000378:metabolism*
chemical_list: D017920:Antiporters; D007328:Insulin; C045885:sodium-lithium countertransporter; D008094:Lithium; D012964:Sodium