Lymphocyte membrane sodium-proton exchange in spontaneously hypertensive rats.
The sodium-proton exchange activity was determined in lymphocytes of spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), and domestic Wistar rats. Uptake of sodium was determined by measuring the osmotic swelling of lymphocytes after activation of the exchanger by suspension of the cells in sodium propionate and consequent intracellular acidification by the permeant weak acid. Fractional swelling (mean +/- SEM) in 16 SHR and 16 WKY was 0.44 +/- 0.03 and 0.35 +/- 0.02, respectively (p less than 0.01). The swelling was partially inhibitable by amiloride and, at 10(-4) M concentration, the amiloride-sensitive swelling was 0.21 +/- 0.02 in SHR and 0.11 +/- 0.01 in WKY (p = 0.001). Progressive extracellular ion substitutions of chloride for propionate or of potassium for sodium showed that the exchange activity was related linearly to cellular acidification; however, the dependence on extracellular sodium displayed saturation characteristics, with the same apparent Km for cells from SHR and WKY and a Vmax of 0.54 +/- 0.03 for SHR and 0.39 +/- 0.02 for WKY (p less than 0.002). External lithium could replace sodium on the exchanger but abolished the differences between strains. Results in the domestic Wistar rats were similar to those of WKY. These results suggest that lymphocytes of the SHR have a greater capacity for sodium uptake through the sodium-proton exchanger, as compared with normotensive strains. If shared by other cells, such an increased capacity could have a pathophysiological role in genetic hypertension. In particular, its presence in proximal renal tubular cells would support the hypothesis of a primary role for the kidney in the pathogenesis of genetic hypertension.
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D011422:Propionates / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D002712:Chlorides; D011422:Propionates; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; D012964:Sodium; D011188:Potassium