Fig. 5: Effects of endothelium-dependent mechanisms on zinc ionophore-dependent vasorelaxation.
From: Zinc drives vasorelaxation by acting in sensory nerves, endothelium and smooth muscle
a Effects of zinc pyrithione with/without endothelium (+/− e), cyclooxygenase inhibition (indomethacin, Indo 3 µM), and capsaicin desensitization (caps, 10 µM followed by washout). b–d Impact of endothelial denudation on zinc-dependent relaxation by clioquinol (b), zinc disulfiram (c), or Zn(DTSM) (d). e Inhibition of nitric oxide synthase with L-NAME (100 µM, p > 0.9999) or soluble guanylate cyclase with ODQ (3 µM, p = 0.9605) had no effect, but the combination of L-NAME and indomethacin decreased the potency of zinc pyrithione in endothelium-intact arteries. f Sildenafil-mediated relaxation potency was decreased by ODQ. g Inhibition of the prostacyclin IP receptor by the selective antagonist CAY10441 (CAY, 1 µM) but not the antagonists of EP2 receptor (PF-04418948, 1 µM) or the prostanoid EP4 receptor (L-161982, 1 µM) decreased the potency of zinc pyrithione. h, i Removal of endogenously available zinc by the selective chelator TPA (30 µM) caused a decrease in the relaxation potency of the nitric oxide-dependent acetylcholine (h), but not the nitric-oxide donor sodium nitroprusside (i). Arteries were contracted with U46619 (U Tone) and responses are expressed as % of the KPSS (124 mM K+)-evoked contractions (Supplementary Table 1). Error bars are SEM (those not shown are contained within the symbol); horizontal error bars are the average EC50. n, number of rats or arteries isolated from separate rats. The control curve in (a) is shown again in (e) for representation. *Statistically significant, two-tailed unpaired Student’s t test of EC50 (T(9) = 2.769 in (b), T(11) = 3.039 in (f), T(10) = 3.754 in (h)); 1-way ANOVA of EC50 [F(9,61) = 27.60, p < 0.0001 in (a, e) and F(3,20) = 3.892, p = 0.0243 in (g)] followed by with Dunnett’s post-test.
