Abstract
The influence of amiloride, a known blocker of Na/H exchange, on the positive inotropic action of α-adrenoceptor stimulation was investigated in isolated rat left atria. Amiloride (300 μm) rapidly (within 10 min) and reversibly abolished the positive inotropic effect of phenylephrine (10 μm; 3 μm propranolol present). Lower concentrations of amiloride inhibited the increase in contractile force caused by phenylephrine in a concentration dependent manner (IC50 of 50 μm). At a concentration of 50 μm, amiloride caused a rightward and downward shift in the concentration-response curve to phenylephrine. Amiloride (10 to 300 μm) affected to only a small extent the increased contractile force in the presence of inotropic interventions known to increase Ca2+ influx via L-type calcium channels (Bay K 8644) and the Na/Ca exchanger (reduced extracellular Na+). To provide evidence that amiloride inhibits the Na/H antiporter intact atria, a contracture that depends on Na+ influx by the Na/H antiporter was examined. Amiloride fully relaxed the contracture induced by ouabain (1 mm) or potassium-free solutions in the identical concentration range over which amiloride inhibited the positive inotropic effect of phenylephrine. Phenylephrine increased the rate of development and the peak amplitude of the amiloride-sensitive contracture (ouabain-induced). The inhibitory action of amiloride on the positive inotropic response to phenylephrine may, in part, be the result of inhibition of the Na/Hantiporter.
Original language | English (US) |
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Pages (from-to) | 391-402 |
Number of pages | 12 |
Journal | Journal of Molecular and Cellular Cardiology |
Volume | 22 |
Issue number | 4 |
DOIs | |
State | Published - Apr 1990 |
Keywords
- Amiloride
- Bay K 8644
- Contracture
- Ouabain
- Phenylephrine
- Positive inotropic agents
- Prazosin
- Rat atria
- Reduced extracellular sodium
- α-Adrenoceptor
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine