Role of soluble guanylyl cyclase in renal afferent and efferent arterioles.

Autor: Wennysia IC; Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Zhao L; Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.; Department of Physiology, School Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China., Schomber T; Research & Development, Bayer AG, Wuppertal, Germany., Braun D; Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Golz S; Research & Development, Bayer AG, Wuppertal, Germany., Summer H; Research & Development, Bayer AG, Wuppertal, Germany., Benardeau A; Research & Development, Bayer AG, Wuppertal, Germany., Lai EY; Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China., Lichtenberger FB; Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Schubert R; Physiology, Medical Faculty, Institute of Theoretical Medicine, University of Augsburg, Augsburg, Germany., Persson PB; Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Xu MZ; Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Patzak A; Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Jazyk: angličtina
Zdroj: American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2021 Feb 01; Vol. 320 (2), pp. F193-F202. Date of Electronic Publication: 2020 Dec 28.
DOI: 10.1152/ajprenal.00272.2020
Abstrakt: Renal arteriolar tone depends considerably on the dilatory action of nitric oxide (NO) via activation of soluble guanylyl cyclase (sGC) and cGMP action. NO deficiency and hypoxia/reoxygenation are important pathophysiological factors in the development of acute kidney injury. It was hypothesized that the NO-sGC-cGMP system functions differently in renal afferent arterioles (AA) compared with efferent arterioles (EA) and that the sGC activator cinaciguat differentially dilates these arterioles. Experiments were performed in isolated, perfused mouse glomerular arterioles. Hypoxia (0.1% oxygen) was achieved by using a hypoxia chamber. Phosphodiesterase 5 (PDE5) and sGC subunits were considerably expressed on the mRNA level in AA. PDE5 inhibition with sildenafil, which blocks cGMP degradation, diminished the responses to ANG II bolus application in AA, but not significantly in EA. Vasodilation induced by sildenafil in ANG II-preconstricted vessels was stronger in EA than AA. Cinaciguat, an NO- and heme-independent sGC activator, dilated EA more strongly than AA after N G -nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) treatment and preconstriction with ANG II. Cinaciguat-induced dilatation of l-NAME-pretreated and ANG II-preconstricted arterioles was similar to controls without l-NAME treatment. Cinaciguat also induced dilatation in iodinated contrast medium treated AA. Furthermore, it dilated EA, but not AA, after hypoxia/reoxygenation. The results reveal an important role of the NO-sGC-cGMP system for renal dilatation and that EA have a more potent sGC activated dilatory system. Furthermore, AA seem to be more sensitive to hypoxia/reoxygenation than EA under these experimental conditions.
Databáze: MEDLINE
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