Effect of Na,K-ATPase inhibition on cytosolic free calcium ions in vascular smooth muscle cells of spontaneously hypertensive and normotensive rats.
OBJECTIVE
To investigate the role of Na(+)-Ca2+ exchange in the regulation of cytosolic free Ca2+ and the pathogenesis of primary hypertension.


METHODS
Cytosolic free Ca2+ ([Ca2+]i) in cultured vascular smooth muscle cells from normotensive and spontaneously hypertensive rats of the Münster strain was measured using the fluorescent dye fura-2 after inhibition of Na+,K+ATPase by ouabain and after addition of angiotensin II.


RESULTS
[Ca2+]i showed a rapid increase together with a depolarization of membrane potential as measured by merocyanine 540. The ouabain-induced increase in [Ca2+]i was blocked in Ca(2+)-free medium and by nifedipine, but incubation with the inhibitor of the Na(+)-Ca2+ exchange, NiCl2, did not diminish the effect of ouabain. Likewise, in Na(+)-free medium the response to ouabain was not suppressed. The angiotensin II-induced changes in [Ca2+]i were diminished in Ca(2+)-free medium and by nifedipine, but enhanced by NiCl2.


CONCLUSIONS
The increase in [Ca2+]i after Na+,K+ ATPase inhibition is not due to a modulation of Na(+)-Ca2+ exchange, but to a Ca2+ influx through Ca2+ channels. Changes in Na(+)-Ca2+ exchange caused by Na+,K+ ATPase inhibition may not play an important role in vascular smooth muscle cells of spontaneously hypertensive rats.
Zhu
Z
Z
Westfälische Wilhelms-Universität, Medizinische Poliklinik, Münster, Germany.
Neusser
M
M
Tepel
M
M
Spieker
C
C
Golinski
P
P
Zidek
W
W
D000818:Animals; D001011:Aorta / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium