Endogenous antimicrobial peptide LL-37 induces human vasodilatation†

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Endogenous antimicrobial peptide LL-37 induces human vasodilatation† I. Berkestedt, A. Nelson, M. Bodelsson British Journal of Anaesthesia Volume 100, Issue 6, Pages 803-809 (June 2008) DOI: 10.1093/bja/aen074 Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 1 Representative recorder tracings illustrating the effect of LL-37 on isolated human omental artery (a) and vein segments (b and c) precontracted with ET-1 (ET). Log molar concentrations are indicated. LL-37 induced no or only weak relaxations in the artery segments (a). In vein segments with intact endothelium, LL-37 induced a relaxation (b), while no or only weak relaxations were induced in endothelium-denuded segments (c). The experiments shown were performed on segments with a comparatively fast response to LL-37 enabling full concentration–response experiments to be performed. British Journal of Anaesthesia 2008 100, 803-809DOI: (10.1093/bja/aen074) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 2 Endothelium dependency of the relaxation induced by LL-37 in isolated human omental vein segments precontracted by a submaximal concentration of ET-1. The LL-37-induced relaxation was markedly reduced after removal of the endothelium (*, two-way repeated measurement anova for the factors LL-37 concentration and endothelium removal followed by Dunnett's post hoc test). Values are means+sem, n=5. British Journal of Anaesthesia 2008 100, 803-809DOI: (10.1093/bja/aen074) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 3 Relaxation induced by LL-37 in isolated segments of human omental vein precontracted by a submaximal concentration of ET-1 in the absence or presence of the nitric oxide synthase inhibitor, Nω-nitro-l-arginine methyl ester (l-NAME, 0.3 mM), potassium chloride (30 mM), or both to inhibit hyperpolarization. l-NAME inhibited the LL-37-induced relaxation by about 30% whereas KCl nearly abolished the LL-37-induced relaxation. Values are means+sem, n=8–11. Asterisk indicates statistically significant difference from control (two-way repeated measurement anova for the factors LL-37 concentration and l-NAME, KCl or both treatment followed by Dunnett's post hoc test). British Journal of Anaesthesia 2008 100, 803-809DOI: (10.1093/bja/aen074) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 4 Relaxation induced by the ALX agonist, WKYMVm (WKY; n=6) or LL-37 (n=5) in isolated segments of human omental vein precontracted by a submaximal concentration of ET-1 in the absence or presence of the selective ALX antagonist WRWWWW (WRW4; 10 μM). WRW4 inhibited the relaxation in response to both WKY and LL-37 (*, two-way repeated measurement anova for the factors WKY or LL-37 concentration and WRW4 treatment followed by Dunnett's post hoc test). Values are means±sem. British Journal of Anaesthesia 2008 100, 803-809DOI: (10.1093/bja/aen074) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 5 Representative recorder tracings illustrating the effect of LL-37 and substance P (SP, 100 nM) on isolated human omental vein segments precontracted with ET-1 (ET) in the presence (a) or absence (b) of the ALX antagonist WRWWWW (WRW4). Log molar concentrations are indicated. LL-37 induced a relaxation in the control segment (b), whereas no relaxation was induced in the presence of WRW4 (a). SP, however, induced a similar relaxation in the presence and absence of WRW4. British Journal of Anaesthesia 2008 100, 803-809DOI: (10.1093/bja/aen074) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 6 Representative agarose gel of RT–PCR products generated from RNA isolated from a vein segment with (+) or without (−) endothelium. Removal of the endothelium reduced the amount of the ALX transcript. The RT–PCR product using the primers for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and a size marker scribed in base pairs (bp) are also shown. British Journal of Anaesthesia 2008 100, 803-809DOI: (10.1093/bja/aen074) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions