Reduced cytosolic free sodium concentration in vascular smooth muscle cells from spontaneously hypertensive rats.
1. Cytosolic free sodium concentration and sodium transport systems were measured in intact cultured vascular smooth muscle cells from spontaneously hypertensive rats of the Münster strain and from normotensive Wistar-Kyoto rats using the sodium-sensitive fluorescent dye sodium-binding benzofuran isophthalate. 2. Resting cytosolic free sodium concentration was significantly lower in vascular smooth muscle cells from spontaneously hypertensive rats than from Wistar-Kyoto rats (10.2 +/- 1.5 mmol/l, n = 26, versus 19.4 +/- 2.5 mmol/l, n = 20, P < 0.01). 3. Inhibition of Na+, K(+)-ATPase by ouabain caused a dose-dependent increase in cytosolic free sodium concentration in spontaneously hypertensive rats and Wistar-Kyoto rats. 4. Activation of Na(+)-Ca2+ exchange by ionomycin increased cytosolic free sodium concentration in both strains. However, the ionomycin-induced increase in cytosolic free sodium concentrations was significantly higher in vascular smooth muscle cells from spontaneously hypertensive rats than from Wistar-Kyoto rats (220 +/- 35% of the resting cytosolic free sodium concentration versus 148 +/- 27%; P < 0.05). The ionomycin-induced increase in cytosolic free sodium concentration was prevented in the absence of external sodium or by inhibition of Na(+)-Ca2+ exchange by NiCl2. 5. Activation of Na(+)-H+ exchange by intracellular acidification of vascular smooth muscle cells with propionic acid increased cytosolic free sodium concentration in each strain (19.6 +/- 5.7 versus 16.3 +/- 3.2 mmol/l). 6. It is concluded that concepts concerning the role of cytosolic free sodium concentration in the pathogenesis of primary hypertension need to be reinvestigated.(ABSTRACT TRUNCATED AT 250 WORDS)
Tepel
M
M
Medizinische Universitäts-Poliklinik, University of Münster, Germany.
Holthues
J
J
Neusser
M
M
Golinski
P
P
Zhu
Z
Z
Mehring
N
N
Zidek
W
W
D000818:Animals; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*
D011422:Propionates; D015759:Ionomycin; D010042:Ouabain; D012964:Sodium