HIGHER NA+-H+ EXCHANGE-RATE AND MORE ALKALINE INTRACELLULAR PH SET-POINT IN ESSENTIAL-HYPERTENSION - EFFECTS OF PROTEIN-KINASE MODULATION IN PLATELETS

被引:45
作者
LIVNE, AA [1 ]
AHARONOVITZ, O [1 ]
PARAN, E [1 ]
机构
[1] BEN GURION UNIV NEGEV, SOROKA MED CTR, HYPERTENS CLIN, IL-84105 BEER SHEVA, ISRAEL
关键词
HYPERTENSION; NA+-H+ EXCHANGE; INTRACELLULAR PH SET-POINT; PHOSPHORYLATION;
D O I
10.1097/00004872-199111000-00006
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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 < 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-mu-mol/l phorbol 12-myristate 13-acetate (PMA) and similar low rates (approximately 0.01) when inhibited by 0.5-mu-mol/l staurosporine. Furthermore, although hypertensive set-point is significantly (P < 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.
引用
收藏
页码:1013 / 1019
页数:7
相关论文
共 42 条
[1]   MODIFIER ROLE OF INTERNAL H+ IN ACTIVATING THE NA+-H+ EXCHANGER IN RENAL MICROVILLUS MEMBRANE-VESICLES [J].
ARONSON, PS ;
NEE, J ;
SUHM, MA .
NATURE, 1982, 299 (5879) :161-163
[2]   KINETIC-PROPERTIES OF THE PLASMA-MEMBRANE NA+-H+ EXCHANGER [J].
ARONSON, PS .
ANNUAL REVIEW OF PHYSIOLOGY, 1985, 47 :545-560
[3]   PLATELET CYTOSOLIC PROTON AND FREE CALCIUM CONCENTRATIONS IN ESSENTIAL-HYPERTENSION [J].
ASTARIE, C ;
LEVENSON, J ;
SIMON, A ;
MEYER, P ;
DEVYNCK, MA .
JOURNAL OF HYPERTENSION, 1989, 7 (06) :485-491
[4]   SPONTANEOUSLY HYPERTENSIVE RAT VASCULAR SMOOTH-MUSCLE CELLS IN CULTURE EXHIBIT INCREASED GROWTH AND NA+/H+ EXCHANGE [J].
BERK, BC ;
VALLEGA, G ;
MUSLIN, AJ ;
GORDON, HM ;
CANESSA, M ;
ALEXANDER, RW .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (03) :822-829
[5]  
BLAUSTEIN MP, 1984, HYPERTENSION, V6, P445, DOI 10.1161/01.HYP.6.4.445
[6]  
CALA PM, 1988, NAPLUS HPLUS EXCHANG, P202
[7]   OKADAIC ACID - A NEW PROBE FOR THE STUDY OF CELLULAR-REGULATION [J].
COHEN, P ;
HOLMES, CFB ;
TSUKITANI, Y .
TRENDS IN BIOCHEMICAL SCIENCES, 1990, 15 (03) :98-102
[8]  
DEWARDENER HE, 1970, KIDNEY INT, V18, P1
[9]   LYMPHOCYTE MEMBRANE SODIUM-PROTON EXCHANGE IN SPONTANEOUSLY HYPERTENSIVE RATS [J].
FEIG, PU ;
DOCCHIO, MA ;
BOYLAN, JW .
HYPERTENSION, 1987, 9 (03) :282-288
[10]   MECHANISMS OF REGULATION OF THE NA+/H+ EXCHANGER [J].
GRINSTEIN, S ;
ROTHSTEIN, A .
JOURNAL OF MEMBRANE BIOLOGY, 1986, 90 (01) :1-12