The influence of pH on the cardiac depressant action of tobramycin.
Tobramycin, like other aminoglycoside antibiotics, is a basic compound which causes a reduction of cardiac contractile force and inhibits the inotropic action of calcium. Its antagonistic action towards calcium had been analysed at different pH values of the solution bathing the rat left atrium. The isometric tension of the electrically driven atrium (4 Hz, 2 ms, supramaximal voltage) in response to cumulative increase in the bath calcium concentration (2.0 to 32.0 mM) was measured in the absence and in the presence of 2.0 x 10(-5) M tobramycin. The increase in pH from 6.6 to 8.2, which decreased the ionization of tobramycin, reduced the cardiac depression. Similar experiments were carried with other cardiac depressants. Thus, the effect of methoxyverapamil (3.5 x 10(-7) M), also a basic compound, was increased at higher values of pH; the acidic pentobarbitone (4 x 10(-5)M) was less effective at more alkaline pH; the cardiac depression of the non-electrolyte ethanol (2 x 10(-4)M) was practically the same over the pH range studied. The time for equilibrium of the antagonism was small for tobramycin, moreover, its antagonism could only be fully reversed by an increase in extracellular calcium. These results suggest a competitive type of antagonism, between the ionized fraction of tobramycin and calcium, for superficial sites of the sarcolemma. The effect of methoxyverapamil, pentobarbitone and ethanol seems to occur at a more internal site of the cardiac cell since the unionized form of the drug is the most active.
Name
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CF
Departmento de Farmacologia, Faculdade de Medicina de Ribeirão Preto-U.S.P., Brazil.
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Antonio
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D000818:Animals; D000889:Anti-Arrhythmia Agents; D004558:Electric Stimulation; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D014031:Tobramycin / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D010424:Pentobarbital; D014031:Tobramycin