Guinea pig aorta rings repeatedly stimulated with phenylephrine (1 microM) in the presence of Krebs solution containing ouabain (0.8 microM) or low K+ (0.5 mM) concentration produced an increase in basal tone. This effect is due to an increase in intracellular Ca2+ as a consequence of Na(+)-K+ATPase pump inhibition induced by receptorial (ouabain) or ion imbalance (low K+) mechanism. We investigated the effect of spironolactone and its metabolites canrenone and potassium canrenoate on the increase in basal tone of guinea pig aorta rings. Spironolactone, canrenone, and potassium canrenoate, in a concentration-dependent manner (3-30 microM), inhibited the increase in basal tone induced by ouabain, most likely acting as antagonist for ouabain binding site on Na(+)-K+ATPase pump. Indeed, this effect appears to be a feature of these drugs since structurally related drugs, such as aldosterone and hydrocortisone, were ineffective. Conversely, all the drugs tested reduced, to a certain degree, the increase in basal tone produced by low K+ Krebs solution, implying that this could be a non-specific effect. Our results may indicate that spironolactone, canrenone, and potassium canrenoate act in hypertension by interfering with mechanisms in which an ouabain-like factor is involved.

Increase in the basal tone of guinea pig thoracic aorta induced by ouabain is inhibited by spironolactone canrenone and potassium canrenoate.

PINTO, Aldo
1996-01-01

Abstract

Guinea pig aorta rings repeatedly stimulated with phenylephrine (1 microM) in the presence of Krebs solution containing ouabain (0.8 microM) or low K+ (0.5 mM) concentration produced an increase in basal tone. This effect is due to an increase in intracellular Ca2+ as a consequence of Na(+)-K+ATPase pump inhibition induced by receptorial (ouabain) or ion imbalance (low K+) mechanism. We investigated the effect of spironolactone and its metabolites canrenone and potassium canrenoate on the increase in basal tone of guinea pig aorta rings. Spironolactone, canrenone, and potassium canrenoate, in a concentration-dependent manner (3-30 microM), inhibited the increase in basal tone induced by ouabain, most likely acting as antagonist for ouabain binding site on Na(+)-K+ATPase pump. Indeed, this effect appears to be a feature of these drugs since structurally related drugs, such as aldosterone and hydrocortisone, were ineffective. Conversely, all the drugs tested reduced, to a certain degree, the increase in basal tone produced by low K+ Krebs solution, implying that this could be a non-specific effect. Our results may indicate that spironolactone, canrenone, and potassium canrenoate act in hypertension by interfering with mechanisms in which an ouabain-like factor is involved.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11386/3017894
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