Kinetics of Na+ and K+ transport in red blood cells of Dahl rats. Effects of age and salt.

Abstract

Blood pressure response to chronic high salt intake and kinetics of red blood cell Na + and K + (Rb + ) transport were studied in salt-sensitive (DS) and salt-resistant (DR) Dahl rats fed a high salt diet (8% NaCl) for 7 weeks from the fifth (young), 12th (adult), or 23rd (old) week of age. The kinetics of ouabain-sensitive Rb + uptake and Na + extrusion were determined in Na + media as a function of both intracellular Na + (Na + ,, 2-8 mmol/1 cells) and extracellular Rb + (Rb + 0 ). In addition, the kinetics of furosemide-sensitive Rb + uptake (related to Rb + 0 ) and the magnitude of the Na + and Rb + leaks were assessed. High salt intake induced hypertension in young and adult but not in old DS rats although red blood cell Na + was slightly increased in all age groups of DS rats fed a high salt diet The kinetic parameters of the Na + -K + pump were similar in DS and DR rats fed a low salt diet Ouabain-sensitive transport rates were not suppressed in erythrocytes of salt hypertensive Dahl rats. Maximal velocities of the Na + -K + pump (related to Na + ,) decreased significantly with age in all groups except in DS rats fed a high salt diet This was compensated by an age-dependent increase in the affinity for Na + , so that no substantial differences in transport rates between young and old rats were seen at physiological cell Na + and plasma K + levels. The maximal velocity of furosemide-sensitive Rb + uptake rose with age in all groups without changes in the affinity for Rb + 0 . High salt intake increased its maximal activity only in DS rats. The Rb + leak was higher in DS relative to DR rats irrespective of salt intake, age, or blood pressure. The Na + leak was elevated in DS rats in which it was augmented by high salt intake. Salt hypertension was, however, not associated with a significant increase of the Na + leak, which was responsible for most alterations of cell Na + content (Hypertension 1990;15:612-627) M any previous studies have indicated the role of genetic factors, salt intake, agedependent susceptibility, and ion transport alterations in the development of hypertension. Nevertheless, the interactions of all these factors have seldom been studied under the same experimental conditions. Dahl salt-sensitive (DS) rats with their age-dependent susceptibility to salt hypertension 1 represent an experimental model that appears to be suitable for such an analysis.From the Institute of Physiology, University of Munich, Munich, Germany.J.Z. was the recipient of a research fellowship from the Alexander von Humboldt Foundation.Presented in part at the 66th Meeting of the German Physiological Society in Wurzburg, September 1988, and published in abstract form (Pflugcrs Arch 1988;412(suppl 1):R51).Address for reprints: Prof. J. Duhm, Institute of Physiology, University of Munich, Pettenkoferstr. 12, D-8000 Munchen 2, FRG.Received May 16, 1989; accepted in revised form February 12, 1990. The information on ion transport in vascular smooth muscle and red blood cells of DS and saltresistant rats (DR) is rath...

Replacement of α1-Na-K-ATPase of Dahl rats by Milan rats lowers blood pressure but does not affect its activity

“…Table 1 shows that none of the components of ion fluxes in erythrocytes from the S rats was affected by the salt diet. These negative results are consistent with previous data of other investigators (27). Also in line with the work of Canessa and coworkers (2), a low-salt diet was used in the further studies on ion transports in erythrocytes from congenic rats.…”

Membrane Ion Transport in Erythrocytes of Salt Hypertensive Dahl Rats and Their F2 Hybrids: the Importance of Cholesterol

“…It should be mentioned that an enhancement of Na leak is a part of major ion transport abnormalities in SHR (6,7,10,25), in LHR and HTG rats (15), and in Sabra (25) and Dahl rats (26). The important role of the Na leak in the pathogenesis of spontaneous forms of experimental hypertension was confirmed by our earlier demonstration of a positive association between the Na leak and blood pressure in both SHR Brown Norway recombinant inbred strains (18) and HTG Lewis F2 hybrids (15).…”

“…This has been demonstrated in humans by epidemiological studies (21)(22)(23) and in rats by genetic analysis (15). Important alterations of erythrocyte Na and K (Rb ) transport have also been reported in salt-sensitive Sabra (24,25) and Dahl rats (26)(27)(28)(29) in which particular abnormalities of the Na -K pump, Na -K cotransport, Na -H exchange and cation leaks were disclosed. Our previous studies suggested that the Na leak is dependent on the genotype, age and salt intake of Dahl rats (26), whereas the Rb leak could be considered a good candidate for a marker of salt sensitivity in Dahl and Sabra rats (30).…”

“…Important alterations of erythrocyte Na and K (Rb ) transport have also been reported in salt-sensitive Sabra (24,25) and Dahl rats (26)(27)(28)(29) in which particular abnormalities of the Na -K pump, Na -K cotransport, Na -H exchange and cation leaks were disclosed. Our previous studies suggested that the Na leak is dependent on the genotype, age and salt intake of Dahl rats (26), whereas the Rb leak could be considered a good candidate for a marker of salt sensitivity in Dahl and Sabra rats (30). It should, however, be considered that salt hypertensive Dahl rats have a typical dyslipidemia characterized by elevated levels of circulating cholesterol (31)(32)(33) and triglycerides (32)(33)(34).…”

Confirmation of mutant alpha 1 Na,K-ATPase gene and transcript in Dahl salt-sensitive/JR rats.

“…As seen in Fig 3 (bottom), at ideal cycling conditions, radiolabeled products are detected prominently only in Dahl R rat genomic DNA samples (R, lanes 4 and 5), in contrast to the low levels of background radiolabeled PCR products detected in Dahl S rat genomic DNA (S, lanes 1 through 3). Intriguingly, the counterpart mutant-specific modified 3' mismatched correction assay was not optimized because the 3' labeling with a-[ 32 (see "Methods"). Briefly, the downstream mRNA priming antisense oligonucleotide was designed with the allele-specific mRNA sequence difference at the 3' end.…”