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In the past three decades, endothelin and endothelin receptor antagonists have received great scientific and clinical interest, leading to the publication of more than 27,000 scientific articles since its discovery. The Thirteenth International Conference on Endothelin (ET-13) was held on September 8-11, 2013, at Tokyo Campus of the University of Tsukuba in Japan. Close to 300 scientists from 25 countries from around the world came to Tokyo to celebrate the anniversary of the discovery of the endothelin peptide discovered 25 years ago at the University of Tsukuba. This article summarizes some of the highlights of the conference, the anniversary celebration ceremony, and particularly the participation of next generation of endothelin researchers in endothelin science and the anniversary celebration. As a particular highlight, next generation endothelin researchers wrote a haiku (a traditional form of Japanese poetry originating from consisting of no more than three short verses and 27 on, or Japanese phonetic units) to describe the magic of endothelin science which they presented to the conference audience at the anniversary ceremony. The text of each haiku - both in its original language together with the English translation - is part of this article providing in an exemplary fashion how poetry can be bridged with science. Finally, we give an outlook towards the next 25 years of endothelin research.

Aims Hypertensive patients develop cardiac hypertrophy and fibrosis with increased stiffness, contractile deficit and altered perfusion. Angiotensin II (AngII) is an important factor in the promotion of this pathology. The effects of AngII are partly mediated by endothelin-1 (ET-1) and transforming growth factor-β. The exact feature of these pathways and the intercellular communications involved remain unclear. In this study, we explored the role of endothelial cell-derived ET-1 in the development of AngII-induced cardiac fibrosis and hypertrophy. Main methods We used mice with vascular endothelial cell specific ET-1 deficiency (VEETKO) and their wild type littermates (WT). Mice were infused for one week with AngII (3.2 mg/kg/day, n = 12) or vehicle (0.15 mol/L NaCl and 1 mmol/L acetic acid, n = 5), using subcutaneous mini-pumps. Hearts were stained with hematoxylin–eosin and masson's trichrome for histology. Cardiac gene expression and protein abundance were measured by Northern Blot, real time PCR and Western Blot. Key findings AngII-induced cardiac hypertrophy, interstitial and perivascular fibrosis were less pronounced in VEETKO mice compared to WT. Blood pressure increased similarly in both genotypes. Expression of connective tissue growth factor, tumor growth factor-β, collagen I and III in response to AngII required endothelial ET-1. Endothelial ET-1 was also necessary to the elevation in protein kinase C δ abundance and ERK1/2 activation. AngII-induced elevation in PKCe abundance was however ET-1 independent. Significance This study underscores the significance of ET-1 from the vasculature in the process of AngII-induced cardiac hypertrophy and fibrosis, independently from blood pressure. Endothelial ET-1 represents therefore a possible pharmacological target.

It has recently been established that a high salt diet leads to sodium storage within the skin of rats and mice. This increase in sodium in the highly vascularized skin results in macrophage infiltration and lymphangiogenesis. While dysfunction in this process has been implicated in salt sensitive hypertension, the mechanisms are poorly understood. Because vascular endothelin-1 (ET-1) is upregulated in response to a high salt diet or hypertonicity, and is a potent chemoattractant, we hypothesized that endothelial derived ET-1 mediates infiltration of immune cells into the skin during chronic high salt intake, thereby allowing sodium clearance from the skin and preventing accumulation. Our data indicate that increasing extracellular concentration of human endothelial cells by 40 mOsm with NaCl, similar to what is seen in the interstitial space of rats placed on a high salt diet, leads to a 50% increase in ET-1 production, a mechanism likely mediated by TonEBP. Furthermore, in response to one week of high salt diet, skin Na/water ratio was elevated in vascular endothelial cell ET-1 knockout mice compared to wild type mice (0.112 ± 0.007 vs. 0.096 ± 0.004 mmol/ml). These data suggest a critical role for ET-1 in preventing the accumulation of sodium in the skin during a high salt intake, an emerging mechanism of the body's ability to buffer blood pressure changes in response to increases in sodium intake.