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This study was performed to examine the effects of endothelin (ET)-1, ET-2, and ET-3 on renin secretion from cultured mouse renal juxtaglomerular (JG) cells. Although different ETs had no consistent effect on basal renin secretion, they equipotently inhibited adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated renin release with a concentration of approximately 3 nM inhibiting 50% of maximal response. ETs did not significantly affect renin release stimulated by the nitric oxide donor sodium nitroprusside (100 microM) or that stimulated by low [2 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] or high (3 mM CaCl2) extracellular calcium. The inhibitory effect of ETs on cAMP-dependent renin secretion was abolished by lowering extracellular calcium concentration to the nanomolar range. However, the action of ETs was not changed by the ETA receptor antagonist BQ-123 (100 nM) and was mimicked by ETB receptor agonists IRL-1620 (1 microM), sarafotoxin S6b (1 microM), and [Ala1,3,11,15]ET-1 (1 microM). All ETs induced calcium oscillations in JG cells that were dependent on extracellular calcium and were associated with prominent calcium-activated chloride currents. These findings suggest that ETs inhibit rather selectively the cAMP-activated pathway of renin secretion through a calcium-sensitive process. The action of ETs on renal JG cells appears to be mediated via ETB receptors and is presumably related to activation of phospholipase C and subsequent events.

Nonthermal treatment with cold atmospheric plasma (CAP) is a promising option for local treatment of chronic-inflammatory and precancerous lesions as well as various mucosal cancer diseases, besides its primary indication for wound healing and antiseptics. Atmospheric pressure plasma jets (APPJs) are versatile plasma sources, some of which are well-characterized and medically approved. The characterization of APPJs, however, is often based on the treatment of simple solutions or even studies on the plasma effluent itself. To better assess the in vivo effects of CAP treatment, this study aims to recapitulate and study the physicochemical tissue-level effects of APPJ treatment on human primary mucosal tissue and tissue models. High resolution on-tissue infrared (IR) thermography and a first-time-performed spatially resolved optical emission spectroscopy (OES) of the APPJ emissions did not identify potentially tissue-harming effects. In this study, electron-spinresonance (ESR) spectroscopy on human tissue samples, treated with different CAP doses, enabled the measurement and the distribution of CAP-derived radicals in the tissues. The results correlate plasma dosage and the generation of radical species with cell viability and cell proliferation of primary human fibroblasts while demonstrating apoptosis-independent antiproliferative cell effects. Moreover, a dose-dependent increase of cells in the G1 phase of the cell cycle was observed, stressing the likely important role of cell cycle regulation for antiproliferative CAP mechanisms. This study introduces suitable methods for CAP monitoring on tissues and contributes to a better understanding of tissue-derived plasma effects of APPJs.

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Non‐thermal plasma treatment is one of the promising options for local anti‐neoplastic treatment of dysplastic lesions and early intraepithelial cancer. Primarily, the antiproliferative properties are driven through the generation of reactive oxygen and nitrogen species. In this study, we investigated the amount and distribution of reactive species generated by a non‐thermally operated electrosurgical argon plasma source using electron spin resonance (ESR) spectroscopy. During the plasma treatment of both, aqueous solution and solid human preputial tissue an increasing amount of different oxygen‐ and carbon‐centered radicals was detected. However, and most probably due to spin trap degradation by the high energy input and the increase of reactive components in aqueous solution, the ESR signal decreased after treatment times exceeding 10 s.