Effect of subthreshold ouabain on the tone of guinea‐pig aortic strips following repeated noradrenaline stimulation

Abstract

1 The effect of ouabain at a concentration (0.8;pM) that does not induce contractile response in guinea-pig aortic strips has been studied on endothelium-denuded strips repeatedly stimulated with 1 AM noradrenaline or 60 mM K+ applied for 5 min every 30 min. 2 The resting tone (i.e. the tone between one noradrenaline stimulation and the following) of the aortic strips exposed to ouabain increased progressively, whereas the control strips (no ouabain) completely relaxed on washout of the agonist. In the aortic strips stimulated by 60 mM K+, the resting tone did not increase.3 The calcium antagonist, verapamil, did not affect the increase in tone, that was nevertheless strictly dependent on external calcium, since the contracted strips completely relaxed on calcium removal and promptly contracted again on calcium readdition. This finding indicates a mechanism independent of voltage-gated calcium channels. 4 Caffeine-induced contractions, taken as a measure of sarcoplasmic reticulum calcium content, were amplified by the presence of ouabain in aortic strips either stimulated by noradrenaline or unstimulated, with a larger increase in the former. 5 These results suggest that the repeated stimulation of guinea-pig aortic strips by noradrenaline in the presence of ouabain, by raising both intracellular Na+ and Ca2+, decreases the ouabain threshold concentration required for contraction, thus increasing the responsiveness of vascular smooth muscle to the glycoside.

Vasorelaxant properties of norbormide, a selective vasoconstrictor agent for the rat microvasculature

“…Norbormide, although less potent than verapamil, is as effective as verapamil in relaxing these vessels. In guinea-pig and rat aorta, norbormide, at concentrations effective against the contraction induced by depolarization, is ineffective on the contraction induced by phenylephrine, a feature that has been observed also for verapamil (Bova et al, 1994) and diltiazem (Cauvin et al, 1984). Likewise, in A7r5 cells both norbormide and verapamil inhibit intracellular calcium transients induced by depolarization, while they do not affect the increase in [Ca2+]i elicited by 5-hydroxytryptamine.…”