EFFECT OF SUBTHRESHOLD OUABAIN ON THE TONE OF GUINEA-PIG AORTIC STRIPS FOLLOWING REPEATED NORADRENALINE STIMULATION

1 The effect of ouabain at a concentration (0.8 muM) that does not ind uce contractile response in guinea-pig aortic strips has been studied on endothelium-denuded strips repeatedly stimulated with 1 muM noradre naline 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, whe reas 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 af fect the increase in tone, that was nevertheless strictly dependent on external calcium, since the contracted strips completely relaxed on c alcium removal and promptly contracted again on calcium readdition. Th is finding indicates a mechanism independent of voltage-gated calcium channels. 4 Caffeine-induced contractions, taken as a measure of sarco plasmic reticulum calcium content, were amplified by the presence of o uabain in aortic strips either stimulated by noradrenaline or unstimul ated, with a larger increase in the former. 5 These results suggest th at the repeated stimulation of guinea-pig aortic strips by noradrenali ne in the presence of ouabain, by raising both intracellular Na+ and C a2+, decreases the ouabain threshold concentration required for contra ction, thus increasing the responsiveness of vascular smooth muscle to the glycoside.