Higher Na(+)-H+ exchange rate and more alkaline intracellular pH set-point in essential hypertension: effects of protein kinase modulation in platelets.
Na(+)-H+ exchange is known to be elevated in essential hypertension. To examine the mechanism of this elevation, we studied a group of 19 male hypertensive patients (mean age 46 years; systolic/diastolic blood pressure 144/99 mmHg), without medication for at least 2 weeks, and a control group of 19 male normotensives (mean age 49 years; systolic/diastolic blood pressure 118/77 mmHg). Na(+)-H+ exchange and intracellular pH set-point, at which the exchange is approximately nil, were studied spectroflurometrically in blood platelets loaded with 2',7'-bis carboxyethyl-5,6-carboxyfluorescein in an isotonic medium containing 60 mmol/l sodium propionate, pH 7.35. The exchange rate (delta pH per 9 s at intracellular pH 7.0) of hypertensives (0.050 +/- 0.005) is significantly greater (P less than 0.001) than the rate of normotensives (0.027 +/- 0.003), but both groups attain similar high (approximately 0.074) rates when phosphorylation is stimulated by 0.5 mumol/l phorbol 12-myristate 13-acetate (PMA) and similar low rates (approximately 0.01) when inhibited by 0.5 mumol/l staurosporine. Furthermore, although hypertensive set-point is significantly (P less than 0.01) more alkaline (7.33 +/- 0.01) than that of the normotensives (7.27 +/- 0.02), both groups attain a similar set-point in the presence of PMA or staurosporine (approximately 7.62 and approximately 7.08, respectively). It is concluded that more extensive phosphorylation of the exchanger, known to be regulated by phosphorylation, is the reason for the modified properties of Na(+)-H+ exchange in essential hypertension, rather than larger numbers of the exchanger per cell.
Livne
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AA
Department of Life Sciences, Soroka Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel.
Aharonovitz
O
O
Paran
E
E
D000470:Alkaloids / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology*; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D011494:Protein Kinases; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate