OBJECTIVES: Nitric oxide (NO) synthesis by NO synthases (NOS) requires oxygen. However, although counterintuitive, NO synthesis is increased in ischemic myocardium. Accordingly, mechanisms independent of the NOS pathway have been suggested to contribute to NO synthesis during ischemia. NO initiates detrimental as well as protective mechanisms in a concentration-dependent manner, thus aggravating or improving the outcome of ischemia. The aim of this study was to measure in situ interstitial NO concentrations in parallel to infarct size in anaesthetized pigs subjected to myocardial ischemia/reperfusion. The contribution of NOS-independent pathways to NO synthesis was studied using NOS blockade. METHODS: Interstitial NO measurements, based on microdialysis combined with the oxyhemoglobin method, were made during 90 min of moderate or severe ischemia and subsequent reperfusion. To examine the effect of NOS inhibition, an initial 30-min ischemic period was followed 60 min later by a second 30-min ischemic period with intracoronary infusion of S-ethyl-isothiourea. RESULTS: During ischemia, the interstitial NO concentration increased for about 30 min and then remained constant at this elevated level. The increase in NO concentration by 253+/-82 nmol/L during moderate and 565+/-169 nmol/L during severe ischemia correlated inversely with subendocardial blood flow (r=-0.76). NOS inhibition increased coronary arterial pressure and decreased the interstitial basal NO concentration and tissue nitrite content. However, it did not diminish the increase in interstitial NO concentration during ischemia. CONCLUSION: NOS-independent pathways are significantly involved in NO synthesis during myocardial ischemia.
OBJECTIVES:Nitric oxide (NO) synthesis by NO synthases (NOS) requires oxygen. However, although counterintuitive, NO synthesis is increased in ischemic myocardium. Accordingly, mechanisms independent of the NOS pathway have been suggested to contribute to NO synthesis during ischemia. NO initiates detrimental as well as protective mechanisms in a concentration-dependent manner, thus aggravating or improving the outcome of ischemia. The aim of this study was to measure in situ interstitial NO concentrations in parallel to infarct size in anaesthetized pigs subjected to myocardial ischemia/reperfusion. The contribution of NOS-independent pathways to NO synthesis was studied using NOS blockade. METHODS: Interstitial NO measurements, based on microdialysis combined with the oxyhemoglobin method, were made during 90 min of moderate or severe ischemia and subsequent reperfusion. To examine the effect of NOS inhibition, an initial 30-min ischemic period was followed 60 min later by a second 30-min ischemic period with intracoronary infusion of S-ethyl-isothiourea. RESULTS: During ischemia, the interstitial NO concentration increased for about 30 min and then remained constant at this elevated level. The increase in NO concentration by 253+/-82 nmol/L during moderate and 565+/-169 nmol/L during severe ischemia correlated inversely with subendocardial blood flow (r=-0.76). NOS inhibition increased coronary arterial pressure and decreased the interstitial basal NO concentration and tissue nitrite content. However, it did not diminish the increase in interstitial NO concentration during ischemia. CONCLUSION: NOS-independent pathways are significantly involved in NO synthesis during myocardial ischemia.
Authors: Mark J Kohr; Angel M Aponte; Junhui Sun; Guanghui Wang; Elizabeth Murphy; Marjan Gucek; Charles Steenbergen Journal: Am J Physiol Heart Circ Physiol Date: 2011-01-28 Impact factor: 4.733
Authors: Hans Erik Bøtker; Derek Hausenloy; Ioanna Andreadou; Salvatore Antonucci; Kerstin Boengler; Sean M Davidson; Soni Deshwal; Yvan Devaux; Fabio Di Lisa; Moises Di Sante; Panagiotis Efentakis; Saveria Femminò; David García-Dorado; Zoltán Giricz; Borja Ibanez; Efstathios Iliodromitis; Nina Kaludercic; Petra Kleinbongard; Markus Neuhäuser; Michel Ovize; Pasquale Pagliaro; Michael Rahbek-Schmidt; Marisol Ruiz-Meana; Klaus-Dieter Schlüter; Rainer Schulz; Andreas Skyschally; Catherine Wilder; Derek M Yellon; Peter Ferdinandy; Gerd Heusch Journal: Basic Res Cardiol Date: 2018-08-17 Impact factor: 17.165
Authors: You-Tang Shen; Christophe Depre; Lin Yan; Ji Yeon Park; Bin Tian; Komal Jain; Li Chen; Yan Zhang; Raymond K Kudej; Xin Zhao; Junichi Sadoshima; Dorothy E Vatner; Stephen F Vatner Journal: Circulation Date: 2008-10-20 Impact factor: 29.690
Authors: Marc W Merx; Simone Gorressen; Annette M van de Sandt; Miriam M Cortese-Krott; Jan Ohlig; Manuel Stern; Tienush Rassaf; Axel Gödecke; Mark T Gladwin; Malte Kelm Journal: Basic Res Cardiol Date: 2013-12-18 Impact factor: 17.165