Modulation of mesenteric collecting lymphatic contractions by {sigma}1-receptor activation and nitric oxide production

Recently, it has been reported that a -receptor antagonist could reduce inflammation-induced edema. Lymphatic vessels play an essential role in removing excess interstitial fluid. We tested the hypothesis that activation of -receptors would reduce or weaken collecting lymphatic contractions. We used isolated, cannulated rat mesenteric collecting lymphatic vessels to study contractions in response to the -receptor agonist afobazole in the absence and presence of different -receptor antagonists. We used RT-PCR and Western blot analysis to investigate whether these vessels express the 1-receptor and immunofluorescence confocal microscopy to examine localization of the 1-receptor in the collecting lymphatic wall. Using N-nitro-l-arginine methyl ester (l-NAME) pretreatment before afobazole in isolated lymphatics, we tested the role of nitric oxide (NO) signaling. Finally, we used 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate fluorescence as an indicator to test whether afobazole increases NO release in cultured lymphatic endothelial cells. Our results show that afobazole (50–150 µM) elevated end-systolic diameter and generally reduced pump efficiency and that this response could be partially blocked by the 1-receptor antagonists BD 1047 and BD 1063 but not by the 2-receptor antagonist SM-21. 1-Receptor mRNA and protein were detected in lysates from isolated rat mesenteric collecting lymphatics. Confocal images with anti-1-receptor antibody labeling suggeste...

Source: AJP: Heart and Circulatory Physiology - October 11, 2017 Category: Cardiology Authors: Trujillo, A. N., Katnik, C., Cuevas, J., Cha, B. J., Taylor-Clark, T. E., Breslin, J. W. Tags: RESEARCH ARTICLE Source Type: research