Fig. 4: Impact of perivascular sensory nerves on zinc ionophore-dependent vasorelaxation in rats and TRPA1 KO mice.
From: Zinc drives vasorelaxation by acting in sensory nerves, endothelium and smooth muscle
a–c Effects of zinc pyrithione with/without perivascular sensory nerve desensitization by capsaicin (caps pretreated), or concomitant zinc chelation with TPA (a), the CGRP receptor antagonist BIBN4096 (BIBN, b), or the TRPA1 channel blockers ruthenium red (RuRed), AM0902 (AM) or HC030031(HC) (c). d Zinc pyrithione activates hTRPA1 expressed in HEK293 cells (measured by the Na+ selective intracellular dye SBFI-AM), but not hTRPV1 or non-transfected (WT) HEK293 cells. e Decreased relaxation potency of zinc pyrithione in isolated mesenteric arteries from TRPA1 KO mice compared to WT mice. f Capsaicin desensitization, BIBN4096 or AM0902 did not affect the relaxation potency of zinc pyrithione in TRPA1 KO mice. g, h Mean arterial pressure (MAP) after an intravenous (i.v.) bolus injections of 0.3, 1, and 3 mg/kg zinc pyrithione (g) and the peak change in MAP (h) in WT (B6129PF2/J) mice. Arteries in a–c, e, and f were contracted with U46619 (U Tone) and responses are expressed as a % of the KPSS (124 mM K+)-evoked contractions (Supplementary Table 3). Error bars are SEM (those not shown are contained within the symbol); horizontal error bars are for the average EC50. n, number of rats, mice or arteries isolated from separate animals. The control curve in (a) and the TRPA1 KO curve in (e) are shown again in (b) and (f), respectively for representation. *Statistically significant, 1-way ANOVA of EC50 [F(9,61) = 27.60, p < 0.0001 in (a, b) and F(3,20) = 15.15, p < 0.0001 in (c)] followed by Dunnett’s post-test vs. control; F(3,19) = 0.0538, p = 0.983 in (d); two-tailed unpaired Student’s t test [T(9) = 2.879 in (e) and T(10) = 2.444 in (h)].
