A mechanical stress increases sodium ion content in vascular smooth muscle cells through a calcium-dependent pathway: prevention by cicletanine via a cyclo-oxygenase product.
The non-laminar (rather turbulent) flow induced by cell washings was able to reversibly increase the sodium ion (Na+) content in cultured A10 aortic smooth muscle cells. Similar changes, although to a lesser extent, were observed in cardiocytes but not in fibroblasts, erythrocytes, thymocytes or macrophages, suggesting that the changes are specific to excitable cells. The increase in vascular sodium content had the following properties: (1) It was inhibited by nitrendipine; (2) it was accompanied by an increase in the free cytosolic Ca2+ content; (3) it was unable to stimulate the sodium pump; and (4) it reflected the qualitative and quantitative composition of the incubation media. These observations suggested that a non-laminar flow is able to open potential-dependent calcium channels, with secondary internalization of high amounts of extracellular ions. These ionic perturbations were blocked by low concentrations of cicletanine; the half-maximal inhibitory concentration (IC50) was about 10(-9) mol/l on internal sodium. The protective effects of cicletanine were inhibited by indomethacin, suggesting that they are mediated by a cyclooxygenase metabolite, perhaps prostacyclin. Captopril and diuretic drugs such as hydrochlorothiazide, furosemide, spironolactone or acetazolamide were unable to protect vascular cells against the harmful effects of cell washings.
Rosati
C
C
INSERM U 7/CNRS UA 318, Hôpital Necker, Paris, France.
Cavalier
S
S
Braquet
P
P
Berthet
P
P
Tarrade
T
T
Ruchoux
M M
MM
Garay
R
R
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003584:Cytological Techniques; D004232:Diuretics / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011725:Pyridines; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013314:Stress, Mechanical
D000959:Antihypertensive Agents; D015220:Calcium Channels; D004232:Diuretics; D011725:Pyridines; D015222:Sodium Channels; D012964:Sodium; C038068:cicletanine; D011451:Prostaglandin-Endoperoxide Synthases