Increase in the basal tone of guinea pig thoracic aorta induced by ouabain is inhibited by spironolactone canrenone and potassium canrenoate.
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.
Sorrentino
R
R
Department of Experimental Pharmacology, University of Naples Federico II, Italy.
Cirino
G
G
Calignano
A
A
Mancuso
F
F
Sorrentino
L
L
Andriuoli
G
G
Pinto
A
A
D000818:Animals; D001013:Aorta, Thoracic; D002191:Canrenoic Acid / Q000494:pharmacology*; D002192:Canrenone / Q000031:analogs & derivatives / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007552:Isotonic Solutions / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010042:Ouabain / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013148:Spironolactone / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D002316:Cardiotonic Agents; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D013148:Spironolactone; D010042:Ouabain; D002192:Canrenone; D002191:Canrenoic Acid; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium