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We described in this paper studies on the modes of operation of cuabain-insensitive sodium transport systems in red cells of normotensive and hypertensive patients. We have extensively investigated the properties of Na countertransport and cotransport in order to clarify whether they are two different proteins or one transport protein with two modes of operation. Several criteria of discrimination between the two pathways are described: They differ in their affinity for Na and Li, sensitivity to several inhibitors, changes in cell volume, and chloride replacement by nitrate. We propose that there are two different transport systems. We have found elevated countertransport in red cells of hypertensive patients in France and in the United States. However, the cotransport system was found elevated in patients in Boston but reduced in patients in Paris. Studies of the modes of operation of the Na-K cotransport system indicate that it can promote K accumulation using an inward sodium gradient. This mode might be more efficient than Na extrusion at the physiological level of Na and K gradients. We interpret our findings of elevated Na-K cotransport in American hypertensive patients as an increased number of transport units functioning as K accumulators. It remains to be determined whether the reduced affinity for internal sodium of the outward cotransport is a defective outward cotransport or else a modulation of this transport system to favor K accumulation.

In erythrocytes, the extrusion of a cell sodium load is accomplished by the ouabain-sensitive sodium-potassium pump and by the furosemide-sensitive sodium-potassium cotransport, which operate against the passive sodium permeability. The precise characterization of these transport pathways requires the determination of the turnover rates of cation translocation and the affinities for subtrates and effectors. The preliminary results of such kinetic study in essential hypertension is reported here.An abnormally low rate of net sodium extrusion by the sodiumpotassium co-transport system was observed in essential hypertensive patients and in a high proportion of their young normotensive offspring. A normal cotransport system found in secondary hypertensive subjects devoid of familial history of hypertension confirmed that the abnormal cotransport system is not the consequence of high blood pressure per se. At the molecular level, the cotransport abnormality seems to be consecutive to a diminished apparent affinity for intracellular Na+.

Our previous observation of a greater increase in erythrocyte Na+ in SHR than in WKY after an acute Na+ load may result either from a genetic membrane property or from a specific plasma influence. In order to elucidate this question, membrane characteristics were compared with or without an acute Na+ load. Na+ transport was measured in Ringer and in plasma on Na+ enriched and K+ depleted red cells. Platelet microviscosity was measured as an index of membrane structural changes. After acute Na+ load a similar reduction of net Na+ extrusion and of K+ influx was observed in both strains. This indicates an inhibition of the Na+,K +-pump. Platelet microviscosity was similarly increased in SHR and WKY. Thus an acute Na+ load induced alterations of membrane properties in both SHR and WKY. The higher erythrocyte Na+ content in SHR stems rather from their intrinsic membrane properties than from a plasma factor.