Increased Na+/H+ antiport activity in the renal brush border membrane of SHR.
Defect in renal salt excretion may play an important role in the pathogenesis of hypertension. We examined sodium (Na+) uptake by brush border membrane (BBM) vesicles of young (6 week old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) of the same age. SHR had lower urinary Na+ excretion (223.1 +/- 9.3 vs. 266.3 +/- 3.7 microEq/day/100 g, N = 8, P less than 0.01) and higher systolic blood pressure (98.9 +/- 1.2 vs. 82.9 +/- 1.8 mm Hg, N = 8, P less than 0.01) than WKY. BBM vesicle Na+ uptake, measured by rapid filtration technique, was higher in SHR when compared to WKY (1.44 +/- 0.03 vs. 1.01 +/- 0.06 nmol/mg/5 sec, N = 4, P less than 0.01). This increase in Na+ influx was apparent only in the present of an outward-directed proton (H+) gradient and was abolished by 1 mM amiloride. BBM permeability to H+ as assessed by acridine orange quenching was not different between SHR and WKY. Kinetic analyses of the amiloride-sensitive BBM Na+ uptake revealed a higher Vmax (2.13 +/- 0.27 vs. 0.70 +/- 0.30 nmol/mg/5 sec, N = 4, P less than 0.01) and a higher km for Na+ (3.55 +/- 0.32 vs. 1.23 +/- 0.14 mM, N = 4, P less than 0.05) in SHR. These findings thus demonstrate an intrinsic derangement in BBM Na+ transport in young SHR which is characterized by increased Na+/H+ antiport activity. This alteration in antiport activity is not attributable to changes in membrane permeability to H+, and is characterized by higher Vmax and km.(ABSTRACT TRUNCATED AT 250 WORDS)
Morduchowicz
G A
GA
Service, Veterans Administration Sepulveda Hospital, California.
Sheikh-Hamad
D
D
Jo
O D
OD
Nord
E P
EP
Lee
D B
DB
Yanagawa
N
N
D000818:Animals; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism*; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011919:Rats, Inbred Strains / Q000378:metabolism*; D012982:Sodium, Dietary / Q000493:pharmacokinetics; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D012982:Sodium, Dietary; D017923:Sodium-Hydrogen Exchangers