Arginine metabolism and nitric oxide turnover in the ZSF1 animal model for heart failure with preserved ejection fraction
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Arginine metabolism and nitric oxide turnover in the ZSF1 animal model for heart failure with preserved ejection fraction. / Büttner, Petra; Werner, Sarah; Baskal, Svetlana; Tsikas, Dimitrios; Adams, Volker; Lurz, Philipp; Besler, Christian; Knauth, Sarah; Bahls, Martin; Schwedhelm, Edzard; Thiele, Holger.
in: SCI REP-UK, Jahrgang 11, Nr. 1, 19.10.2021, S. 20684.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Arginine metabolism and nitric oxide turnover in the ZSF1 animal model for heart failure with preserved ejection fraction
AU - Büttner, Petra
AU - Werner, Sarah
AU - Baskal, Svetlana
AU - Tsikas, Dimitrios
AU - Adams, Volker
AU - Lurz, Philipp
AU - Besler, Christian
AU - Knauth, Sarah
AU - Bahls, Martin
AU - Schwedhelm, Edzard
AU - Thiele, Holger
N1 - © 2021. The Author(s).
PY - 2021/10/19
Y1 - 2021/10/19
N2 - Endothelial dysfunction and altered nitric oxide (NO) metabolism are considered causal factors in heart failure with preserved ejection fraction (HFpEF). NO synthase activity depends on the availability of arginine and its derivatives. Thus, we analyzed arginine, associated metabolites, arginine-metabolizing enzymes and NO turnover in 20-week-old female healthy lean (L-ZSF1) and obese ZSF1 rats (O-ZSF1) with HFpEF. Serum, urine and lysates of liver, kidney and heart were analyzed. There were significantly lower lysine (- 28%), arginine (- 31%), homoarginine (- 72%) and nitrite (- 32%) levels in serum of O-ZSF1 rats. Ornithine (+ 60%) and citrulline (+ 20%) levels were higher. Similar results were found in the heart. Expression of arginine consuming enzymes in liver and kidney was unchanged. Instead, we observed a 5.8-fold higher arginase 1 expression, presumably of granulocyte origin, in serum and > fourfold increased cardiac macrophage invasion in O-ZSF1. We conclude that inflammatory cells in blood and heart consume arginine and probably homoarginine via arginase 1 and inducible NO synthase and release ornithine and citrulline. In combination with evidence for decreased NO turnover in O-ZSF1 rats, we assume lower arginine bioavailability to endothelial NO synthase.
AB - Endothelial dysfunction and altered nitric oxide (NO) metabolism are considered causal factors in heart failure with preserved ejection fraction (HFpEF). NO synthase activity depends on the availability of arginine and its derivatives. Thus, we analyzed arginine, associated metabolites, arginine-metabolizing enzymes and NO turnover in 20-week-old female healthy lean (L-ZSF1) and obese ZSF1 rats (O-ZSF1) with HFpEF. Serum, urine and lysates of liver, kidney and heart were analyzed. There were significantly lower lysine (- 28%), arginine (- 31%), homoarginine (- 72%) and nitrite (- 32%) levels in serum of O-ZSF1 rats. Ornithine (+ 60%) and citrulline (+ 20%) levels were higher. Similar results were found in the heart. Expression of arginine consuming enzymes in liver and kidney was unchanged. Instead, we observed a 5.8-fold higher arginase 1 expression, presumably of granulocyte origin, in serum and > fourfold increased cardiac macrophage invasion in O-ZSF1. We conclude that inflammatory cells in blood and heart consume arginine and probably homoarginine via arginase 1 and inducible NO synthase and release ornithine and citrulline. In combination with evidence for decreased NO turnover in O-ZSF1 rats, we assume lower arginine bioavailability to endothelial NO synthase.
U2 - 10.1038/s41598-021-00216-7
DO - 10.1038/s41598-021-00216-7
M3 - SCORING: Journal article
C2 - 34667218
VL - 11
SP - 20684
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
IS - 1
ER -
