The erythrocyte Na,K,Cl cotransporter and its circulating inhibitor in Dahl salt-sensitive rats.
BACKGROUND
Abnormal Na,K,Cl cotransport is thought to be a pathogenic factor in Dahl salt-sensitive rat models, but the only direct evidence for this is an increased cotransport activity found in erythrocytes from salt-loaded Dahl salt-sensitive rats.


OBJECTIVE
To re-examine erythrocyte cotransport fluxes and a circulating cotransport inhibitory factor (CIF) in inbred Dahl rats maintained on a low (0.2%) salt diet. Cotransport fluxes were investigated both under basal conditions and after stimulation by cell shrinking.


METHODS
Blood was drawn from 12 male Dahl salt-sensitive and 12 Dahl salt-resistant rats of the inbred John Rapp strain. Erythrocyte Na,K,Cl cotransport activity was equated to the bumetanide-sensitive fluxes of sodium, rubidium or lithium. Plasma CIF activity was tested in human erythrocytes.


RESULTS
In Dahl salt-sensitive rats: (1) plasma CIF activity (5.7+/-0.4 units/ml) was modestly higher than in Dahl salt-resistant rats (2.97+/-0.12 units/ml, P < 0.0001), but much lower than that previously found in salt-loaded Dahl salt-sensitive rats (16.1 units/ml), and (2) erythrocytes exhibited a similar bumetanide-sensitive sodium efflux (rate constant 0.056+/-0.008 h(-1)) as in Dahl salt-resistant rats (0.047+/-0.007 h(-1)). Following hypertonic shock, the bumetanide-sensitive rubidium influx reacted more to cell shrinkage in Dahl salt-sensitive than in Dahl salt-resistant erythrocytes (cell volume decrease required to stimulate bumetanide-sensitive rubidium influx by 4000 micromol/l cells per h=-4.04+/-0.36 versus -5.89+/-0.44 fl, respectively; P< 0.01).


CONCLUSIONS
When fed a low-salt diet, Dahl salt-sensitive rats present slightly increased plasma CIF levels and normal erythrocyte cotransport fluxes under basal conditions, but an increased response to a hypertonic shock. Therefore, if there is any primary cotransport abnormality in Dahl salt-sensitive rats, it appears to be restricted to the renal Na,K,Cl cotransporter BSC1 isoform. Alternatively, any such change may be the consequence of abnormal regulation by osmolarity-dependent mechanisms.
Alvarez-Guerra
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INSERM U400, Faculté de Médecine, Créteil, France.
Nazaret
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C
Garay
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D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000097:blood*; D002712:Chlorides / Q000097:blood; D004232:Diuretics / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000097:blood*; D045283:Natriuretic Agents / Q000097:blood*; D011188:Potassium / Q000097:blood; D051381:Rats; D020303:Rats, Inbred Dahl; D012964:Sodium / Q000097:blood; D012965:Sodium Chloride / Q000494:pharmacology; D028021:Sodium-Potassium-Chloride Symporters
D002352:Carrier Proteins; D002712:Chlorides; D004232:Diuretics; D008565:Membrane Proteins; D045283:Natriuretic Agents; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; D012965:Sodium Chloride; D012964:Sodium; D011188:Potassium