Figure 3 | Scientific Reports

Figure 3

From: Antagonism of Nav channels and α1-adrenergic receptors contributes to vascular smooth muscle effects of ranolazine

Figure 3

Implication of Nav channels in the vascular response to ranolazine in rat aortic rings.

(A) Ranolazine reversed the contraction induced by veratridine in the presence and in the absence of the endothelium. Typical recordings of variations in isometric tension during the following protocols were shown: the presence or absence of endothelium was first confirmed by either the induced vasorelaxation or the lack of an effect of 1 μM acetylcholine (Ach) on the contraction evoked by a submaximal concentration of Phe (10 μM), then after a wash period, ranolazine was cumulatively added (0.1 to 200 μM) after the contraction induced by veratridine (100 μM) was established. Graph summarizes dose-response curves to ranolazine (n = 10 aortas; each protocol performed in duplicate). (B) The effect of ranolazine was evaluated in the absence of endothelium on KCl-induced contraction under basal conditions (upper panels) and after α-adrenergic blockade with prazosin (lower panels). Typical recordings illustrate variations in isometric tension after the addition of cumulative doses of KCl (1 to 40 mM) in the absence (left) and in the presence of ranolazine (20 μM) (right). Graphs summarize the dose-response curves obtained for KCl. Data are expressed as the percentage of the maximal contraction induced by KCl (n = 15 aortas). The inset shows the maximal KCl-induced contraction (in g) for the control and in the presence of ranolazine and nifedipine (1 μM). (C) (Left and middle panels) The effects of ranolazine on KCl-induced contraction were evaluated in de-endothelialized aortic rings in the presence of prazosin, after inhibition of the Nav with TTX (1 μM) or of the NCX with KB-R7943 (10 μM). Dose-response curves were compared for KCl concentrations below 10 mM in the absence and in the presence of ranolazine. (Right panel) Graph shows the maximal contractions (in g) induced, in the presence of prazosin (10 μM), by KCl for the control and in the presence of TTX, ranolazine, KBR or nifedipine (1 μM) (n = 6 aortas, each protocol performed in duplicate). *p < 0.05, **p < 0.01, ***p < 0.001, two-way Anova for dose responses and one-way Anova for maximal contractions followed by Bonferroni post-test.

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