[Beneficial effects of xipamide on pH and Ca2+ ions of cardiac cells].
We have shown that xipamide is the only antihypertensive agent able to selectively inhibit the anion exchanger (AE), a transport system translocating (i) chloride and bicarbonate (thus participating to internal pH), but also (ii) Na+ as NaCO3-(which could explain the natriuretic effect of xipamide). On the other hand, Ollivier (Val de Grâce, Paris) has shown that xipamide exerts a beneficial action on heart by favoring left ventricular relaxation in essential hypertensive patients exhibiting cardiac hypertrophy. In order to understand this clinical effect, we have studied the effect of xipamide on pH and cytosolic free calcium in cultured Rat cardiocytes (H9c2 line). pHi was measured at equilibrium using 14C-DMO and cytosolic free calcium was measured spectrofluorimetrically with Fura2 (Shimadzu RF 5000). 1) The presence of bicarbonate induced a 0.39 +/- 0.14 (mean +/- SD; n = 3) alkalinization; final pHi was 7.08 +/- 0.15 (n = 8). Nor 20 microM DIDS (specific AE inhibitor), neither 50 microM xipamide were able to modify this result. This suggests that the alkalinization is not due to the anion exchanger. 2) After preincubation in the presence of 0.5 microM DIDS, we observed a 0.35 +/- 0.21 acidification (n = 4). Conversely, 0.5 microM xipamide induced a 0.22 +/- 0.16 alkalinization (n = 4). 3) Xipamide (0.5-500 microM) increased the internal K/Na ratio (at 0.5 microM, delta = 3.1 +/- 0.2; n = 3); this was mainly due to internal K+ increase.(ABSTRACT TRUNCATED AT 250 WORDS)
Hannaert
P
P
INSERM U 7, hôpital, Necker, Paris.
Christen
M O
MO
Wierzbicki
N
N
Garay
R
R
D000818:Animals; D001639:Bicarbonates; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry; D003971:Diastole; D006321:Heart / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D009206:Myocardium / Q000737:chemistry; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism; D014988:Xipamide / Q000494:pharmacology*
D001639:Bicarbonates; D014988:Xipamide; D012964:Sodium; D011188:Potassium; D002118:Calcium
Effets bénéfiques du xipamide sur le pH et le Ca2+ des cardiocytes.